Recombinant chalcomycin polyketide synthase and modifying genes

ABSTRACT

Domains of chalcomycin polyketide synthases and modification enzymes and polynucleotides encoding them are provided. Methods to prepare chalcomycin in pharmaceutically useful quantities are described, as are methods to prepare chalcomycin analogs and other polyketides using the polynucleotides encoding chalcomycin polyketide synthase domains or modifying enzymes.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims benefit of U.S. provisional patent application Nos. 60/405,194 (filed Aug. 21, 2002); 60/420,994 (filed Oct. 24, 2002); and 60/493,966 (filed Aug. 8, 2003) each of which is incorporated herein by reference in its entirety.

STATEMENT OF GOVERNMENT INTEREST

[0002] Subject matter disclosed in this application was made, in part, with government support under NIH Grant No. R43 CA AI50305. As such, the United States government may have certain rights in this invention.

FIELD OF THE INVENTION

[0003] The invention relates to recombinant polynucleotides that encode polypeptides or domains of the chalcomycin polyketide synthase gene cluster. Accordingly, the present invention is directed to the production of chalcomycin PKS enzymes, to polynucleotides that encode such enzymes, and to host cells that contain such polynucleotides. Further enhancements in the biological activities of chalcomycin and other polyketides, through production of derivatives thereof, is also made possible according to the practice of the invention by providing P450 hydroxylases that provide attachment points on the polyketide molecule for further modifications. Thus the present invention relates to the fields of molecular biology, chemistry, recombinant DNA technology, medicine, animal health, and agriculture.

BACKGROUND OF THE INVENTION

[0004] Polyketides represent a large family of diverse compounds synthesized from 2 carbon units through a series of condensations and subsequent modifications. Polyketides occur in many types of organisms including fungi and mycelial bacteria, in particular the actinomycetes. An appreciation for the wide variety of polyketide structures and for their biological activities, may be gained upon review of the extensive art, for example, published PCT Patent Publication WO 95/08548 and U.S. Pat. Nos. 5,672,491 and 6,303,342

[0005] Polyketides are synthesized in nature by polyketide synthases (“PKS”). The Type I or modular PKS comprise a set of separate catalytic active sites; each active site is termed a “domain”, and a set thereof is termed a “module”. One module exists for each cycle of carbon chain elongation and modification. FIG. 9 of aforementioned WO95/08548 depicts a typical Type I PKS, in this case 6-deoxyerythronolide B synthase (“DEBS”), which is involved in the production of erythromycin. Six separate modules, each catalyzing a round of condensation and modification of a 2-carbon unit, are present in DEBS. The number and type of catalytic domains that are present in each module varies based on the needed chemistry, and the total of 6 modules is provided on 3 separate polypeptides (designated DEBS-1, DEBS-2, and DEBS-3, with 2 modules per each polypeptide). Each of the DEBS polypeptides is encoded by a separate open reading frame (gene), see Caffrey et al., FEBS Letters, 304, pp. 205, 1992. DEBS provides a representative example of a Type I PKS. In DEBS, modules 1 and 2 reside on DEBS-1, modules 3 and 4 on DEBS-2, and modules 5 and 6 on DEBS-3, wherein module 1 is defined as the first module to act on the growing polyketide backbone, and module 6 the last.

[0006] The minimal PKS module is typified by module 3 of DEBS which contains a ketosynthase (“KS”) domain, an acyltransferase (“AT”) domain, and an acyl carrier protein (“ACP”) domain. These three enzyme activities are sufficient to activate a 2-carbon extender unit and attach it to the growing polyketide molecule. Additional domains that may be included in a module relate to reactions other than the actual condensation, and include domains for a ketoreductase activity (“KR”), a dehydratase activity (“DH”), and an enoylreductase activity (“ER”). With respect to DEBS-1, the first module thereof also contains an additional set of the AT and ACP activities because that module catalyzes initial condensation, and so begins with a “loading domain” (sometimes referred to as a loading module) that contains an AT and ACP, that bind the starter unit. The “finishing” of the 6-deoxyerythronolide molecule is regulated by a thioesterase activity (“TE”) in module 6 that catalyzes cyclization of the macrolide ring during release of the product of the PKS.

[0007] PKS genes can be engineered in a variety of ways to achieve biosynthesis of polyketides. For instance, PKS genes can be inserted into a heterologous host to make a polyketide in a host that does not make it naturally. Polyketides can also be made by hybrid or otherwise altered PKSs or polyketide biosynthetic gene clusters. Also, polyketides can be overproduced by increasing the pools of available starting polyketide biosynthetic precursors and by other means. See U.S. Pat. Nos. 5,672,491; 5,962,290; 6,080,555; 6,391,594; and 6,221,641 and PCT Patent Publications 00/47724, 01/27306, and 01/31035.

[0008] Chalcomycin is a 16-membered macrolide antibiotic produced by some strains of Streptomyces bikiniensis and possesses a broad spectrum of antimicrobial activity. Certain naturally occurring derivatives of chalcomycin produced by other Streptomyces organisms also have antimicrobial activity. For instance, the 8-deoxy chalcomycin derivative produced by Streptomycin hirsutus has antimicrobial activity against gram-positive bacteria. Chalcomycin has two modifying sugar molecules, D-mycinose and D-chalcose, the former being subject to post-glycosylation modification by O-methylation at two positions. For additional information regarding chalcomycin, see Woo, P. W. K. et al., J.A.C.S., 1962, 84, 1512; 1964, 86, 2724; 2726; Celmer, W. D., J. A. C. S., 1965, 87, 1801; Omura, S. et al., J. A. C. S., 1975, 97, 4001; Neszmelyi, A. et al., Chem. Comm., 1976, 97; Jardim, M. E. et al., Int. J. Mass Spectrom. Ion Phys., 1983, 48, 189; Hauske, J. R. et al., J. O. C., 1986, 51, 2808; Kim, S. D. et al., J. Antibiot., 1996, 49, 955; Woo, P. W. K. et al., Tetrahedron, 1996, 52, 3857 and Goo, Y. M. et al., J. Antibiot., 1997, 50, 85.

[0009] The chemical structure of chalcomycin, shown without stereochemistry, is provided by formula I below.

[0010] Chalcomycin is synthesized by a Type I or modular PKS and modification enzymes. Post-PKS modification reactions include P450 oxidation at three sites to add hydroxyl groups and glycosylation at the C5 hydroxyl to add D-chalcose, and at the C20 hydroxyl to add allose, which is then methylated at two positions to yield D-mycinose.

[0011] There is a need for recombinant nucleic acids, host cells, and methods of using those host cells to produce polyketides including but not limited to chalcomycin and chalcomycin analogs. These and other needs are met by the materials and methods provided by the present invention.

SUMMARY OF THE INVENTION

[0012] The present invention provides recombinant nucleic acids encoding polyketide synthases and polyketide modification enzymes. The recombinant nucleic acids of the invention are useful in the production of polyketides, including but not limited to chalcomycin and chalcomycin analogs and derivatives in recombinant host cells. The biosynthesis of chalcomycin is performed by a modular PKS and polyketide modification enzymes. The chalcomycin synthase is made up of several proteins, each having one or more modules. The modules have domains with specific synthetic functions.

[0013] The present invention also provides domains and modules of the chalcomycin PKS and corresponding nucleic acid sequences encoding them and/or parts thereof. Such compounds are useful in the production of hybrid PKS enzymes and the recombinant genes that encode them.

[0014] The present invention also provides modifying genes of chalcomycin biosynthetic gene cluster in recombinant form, including but not limited to isolated form and incorporated into a vector or the chromosomal DNA of a host cell. The present invention also provides recombinant P450 hydroxylases that provide hydroxyl attachment points useful for further chemical modification. The P450 hydroxylases of the present invention include ChmHI, ChmPI and ChmPII hydroxylases.

[0015] The present invention also provides recombinant host cells that contain the nucleic acids of the invention. In one embodiment, the host cell provided by the invention is a Streptomyces host cell that produces a chalcomycin modification enzyme and/or a domain, module, or protein of the chalcomycin PKS. Methods for the genetic manipulation of Streptomyces are described in Kieser et al, “Practical Streptomyces Genetics,” The John Innes Foundation, Norwich (2000), which is incorporated herein by reference in its entirety.

[0016] Accordingly, there is provided a recombinant PKS wherein at least 10, 15, 20, or more consecutive amino acids in one or more domains of one or more modules thereof are derived from one or more domains of one or more modules of chalcomycin polyketide synthase. Preferabiy at least an entire domain of a module of chalcomycin synthase is included. Representative chalcomycin PKS domains useful in this aspect of the invention include, for example, KR, DH, ER, AT, ACP and KS domains. In one embodiment of the invention, the PKS is assembled from polypeptides encoded by DNA molecules that comprise coding sequences for PKS domains, wherein at least one encoded domain corresponds to a domain of chalcomycin PKS. In such DNA molecules, the coding sequences are operably linked to control sequences so that expression therefrom in host cells is effective. In this manner, chalcomycin PKS coding sequences or modules and/or domains can be made to encode PKS to biosynthesize compounds having antibiotic or other useful bioactivity other than chalcomycin.

[0017] These and other aspects of the present invention are described in more detail in the Detailed Description of the Invention, below.

BRIEF DESCRIPTION OF THE DRAWINGS

[0018]FIG. 1 illustrates the structure of the chalcomycin PKS biosynthetic gene cluster, and cosmids pKOS146.185.1 and pKOS146.185.10, which contain insert DNA encompassing the chalcomycin PKS gene cluster and associated modification enzyme genes. Abbreviations: ACP, acyl carrier protein; chm, chalcomycin gene; Orf, open reading frame.

[0019]FIG. 2 shows proposed pathways for post-PKS modification of the chalcomycin-spiramycin hybrid PKS macrolide product.

DETAILED DESCRIPTION OF THE INVENTION

[0020] The invention provides recombinant materials for the production of polyketides. In an aspect, the present invention provides recombinant nucleic acids encoding polyketide synthases that contain all or a portion of the chalcomycin PKS. The biosynthesis of chalcomycin is performed by a modular PKS and modification enzymes. The chalcomycin synthase is made up of five proteins, each having one or more modules, each module comprising domains with specific synthetic functions. Thus, the present invention also provides the domains and modules of the chalcomycin PKS and corresponding nucleic acid sequences encoding them in recombinant form.

[0021] Modifying genes of the chalcomycin biosynthetic gene cluster are also provided, including but not limited to the genes for the ChmHI, ChmPI and ChmPII P450 hydroxylases that provide hydroxyl attachment points useful for further chemical modification.

[0022] Methods and host cells for using these genes to produce or modify a polyketide in recombinant host cells are also provided.

[0023] The nucleotide sequences encoding chalcomycin PKS and modifying proteins of the present invention were isolated from Streptomyces bikiniensis NRRL 2737 (obtained from the Agricultural Research Service Culture Collection, National Center for Agricultural Utilization Research, Peoria, Ill. USA). The chalcomycin PKS gene cluster and modifying genes are contained in cosmids pKOS 146.185.1 and pKOS146.185.10. The cloning and characterization of the chalcomycin PKS gene cluster is described in Example 1, infra. pKOS146-185.1 was deposited under the terms of the Budapest Treaty with the American Type Culture Collection, 10801 University Blvd., Manassas, Va., 20110-2209, on Feb. 19, 2003, with accession number PTA-4961. pKOS146-185.10 was deposited under the terms of the Budapest Treaty with the American Type Culture Collection, 10801 University Blvd., Manassas, Va., 20110-2209, on Feb. 19, 2003, with accession number PTA-4962.

[0024] Given the valuable properties of chalcomycin and its modifying enzymes, means to produce useful quantities thereof and derivatives or analogs of chalcomycin are valuable. Further, the chalcomycin modifying enzymes can also be used to modify other polyketides and produce derivatives thereof with enhanced solubility and/or bioactivity, for instance as antibiotics, and/or sites for further enzymatic or chemical modification. The nucleotide sequences of the chalcomycin biosynthetic gene cluster encoding chalcomycin PKS and modifying enzymes, and domains and/or modules of the PKS can be used, for example, to make antibiotics or other useful compounds in addition to chalcomycin, and in host cells in addition to Streptomyces bikiniensis.

[0025] There is a need for recombinant nucleic acids, host cells, and methods of expressing those nucleic acids in host cells resulting in production of chalcomycin and or its analogs or derivatives, and modifying enzymes, such as the cytochrome P450 hydroxylases that specifically attach hydroxyl groups on the resulting aglycone (which can then be used as attachment points for further modifications). The modifying P450's from the chalcomycin PKS cluster of the present invention can be used to make compounds in a host that does not naturally produce such compounds. These and other needs are met by the materials and methods of the present invention

[0026] In one aspect of the invention, purified and isolated DNA molecules are provided that comprise one or more coding sequences for one or more domains or modules of chalcomycin synthase. Examples of such encoded domains include chalcomycin synthase KR, DH, ER, AT, ACP, and KS domains. In one aspect, the invention provides DNA molecules in which the complete set of chalcomycin PKS-encoding sequences are operably linked to expression control sequences that are effective in suitable host cells to produce chalcomycin and/or its analogs or derivatives. In one aspect, the invention provides polypeptides comprising a portion of the coding sequences for the proteins of the chalcomycin synthase.

[0027] Table 2 in Example 1 provides a description of genes in the chalcomycin PKS gene (i.e., SEQ ID NO:1 and subsequences encoding modules, domains and ORFs, e.g., as indicated), as well as encoded proteins (including SEQ ID. NOS: 2-43) or domains. It will be apparent from Table 2, and FIGS. 1 and 2, which DNA strand comprises the coding sequence for a protein (i.e., the strand having the sequence of SEQ ID NO:1, or its complement.

[0028] In one aspect, the invention provides an isolated or recombinant DNA molecule comprising a nucleotide sequence that encodes at least one polypeptide, alternatively at least one module, alternatively at least one domain, involved in the biosynthesis of a chalcomycin. In one aspect, the invention provides the present invention provides an isolated or recombinant DNA molecule comprising a nucleotide sequence that encodes at least one polypeptide, alternatively at least one module, alternatively at least one domain, involved in the biosynthesis of a chalcomycin. The invention also provides polypeptides comprising PKS interpolypeptide linker sequences, and polynucleotides encoding such linker sequences. Also provided by the invention are polypeptides comprising intrapolypeptide linker sequences, and polynucleotides encoding such linkers.

[0029] In one aspect, the invention provides an isolated or recombinant DNA molecule comprising a sequence identical or substantially similar to at least one subsequence of SEQ ID NO:1 or its complement. In an embodiment the subsequence comprises a sequence encoding a chalcomycin PKS domain or module. In an aspect, the invention provides a recombinant DNA molecule that encodes a polypeptide, module or domain derived from a chalcomycin polyketide synthase (PKS) gene cluster. In this context, a polypeptide, module or domain is derived from a chalcomycin polyketide synthase (PKS) gene cluster when it is encoded by a DNA with substantial sequence identity to the corresponding coding region of the S. bikiniensis chalcomycin gene cluster. For example, in an embodiment, the DNA encoding sequence of the polypeptide, module or domain hybridizes under stringent conditions to a nucleic acid having the sequence of SEQ ID NO:1 (or its complement). Generally, such a polypeptide, module or domain is biologically active, i.e., has at least one enzymatic activity chracteristic of the polypeptide, module or domain encoded exactly by corresponding sequence of SEQ ID NO:1 or its complement. The biological activity of a polypeptide of the invention can be measured by methods well known to the art.

[0030] In one aspect, the invention provides the present invention provides an isolated or recombinant DNA molecule comprising a nucleotide sequence that encodes an open reading frame, module or domain having an amino acid sequence identical or substantially similar to an ORF, module or domain encoded by SEQ ID NO:1 or its complement. Generally, a polypeptide, module or domain having a sequence substantially similar to a reference sequence has substantially the same activity as the reference protein, module or domain (e.g., when integrated into an appropriate PKS framework using methods known in the art). In certain embodiments, one or more activities of a substantially similar polypeptide, module or domain are modified or inactivated as described below.

[0031] In one aspect, the invention provides an isolated or recombinant DNA molecule comprising a nucleotide sequence that encodes at least one polypeptide, module or domain encoded by SEQ ID NO:1, e.g., a polypeptide, module or domain involved in the biosynthesis of a chalcomycin, wherein said nucleotide sequence comprises at least 20, 25, 30, 35, 40, 45, or 50 contiguous base pairs identical to a sequence of SEQ ID NO:1 or its complement. In one aspect, the invention provides an isolated or recombinant DNA molecule comprising a nucleotide sequence that encodes at least one polypeptide, module or domain encoded by SEQ ID NO:1, e.g., a polypeptide, module or domain involved in the biosynthesis of a chalcomycin, wherein said polypeptide, module or domain comprises at least 10, 15, 20, 30, or 40 contiguous residues of a corresponding polypeptide, module or domain encoded by SEQ ID NO:1 or its complement.

[0032] In a related aspect, the invention provides a recombinant DNA molecule, comprising a sequence of at least about 200, optionally at least about 500, basepairs with a sequence identical or substantially identical to a protein encoding region of SEQ ID NO:1. In an embodiment, the DNA molecule encodes a polypeptide, module or domain derived from a chalcomycin polyketide synthase (PKS) gene cluster.

[0033] It will be understood that SEQ ID NO:1 was determined using the inserts of pKOS 146.185.1 and pKOS146-185.10. Accordingly, the invention provides an isolated or recombinant DNA molecule comprising a sequence identical or substantially similar to a ORF encoding sequence of the insert of pKOS 146.185.1 or pKOS146-185.10.

[0034] Those of skill will recognize that, due to the degeneracy of the genetic code, a large number of DNA sequences encode the amino acid sequences of the domains, modules, and proteins of the chalcomycin PKS, the enzymes involved in chalcomycin modification and other polypeptides encoded by the genes of the chalcomycin biosynthetic gene cluster. The present invention contemplates all such DNAs. For example, it may be advantageous to optimize sequence to account for the codon preference of a host organism. The invention also contemplates naturally occurring genes encoding the chalcomycin PKS and tailoring enzymes that are polymorphic or other variants. In addition, it will be appreciated that polypeptide, modules and domains of the invention may comprise one or more conservative amino acid substitutions relative to the polypeptides encoded by SEQ ID NO: 1, such as, for example, conservative substitutions include aspartic-glutamic as acidic amino acids; lysine/arginine/histidine as basic amino acids; leucine/isoleucine, methionine/valine, alanine/valine as hydrophobic amino acids; serine/glycine/alanine/threonine as hydrophilic amino acids.

[0035] As used herein, the terms “substantial identity,” “substantial sequence identity,” or “substantial similarity” in the context of nucleic acids, refers to a measure of sequence similarity between two polynucleotides. Substantial sequence identity can be determined by hybridization under stringent conditions, by direct comparison, or other means. For example, two polynucleotides can be identified as having substantial sequence identity if they are capable of specifically hybridizing to each other under stringent hybridization conditions. Other degrees of sequence identity (e.g., less than “substantial”) can be characterized by hybridization under different conditions of stringency. “Stringent hybridization conditions” refers to conditions in a range from about 5° C. to about 20° C. or 25° C. below the melting temperature (Tm) of the target sequence and a probe with exact or nearly exact complementarity to the target. As used herein, the melting temperature is the temperature at which a population of double-stranded nucleic acid molecules becomes half-dissociated into single strands. Methods for calculating the Tm of nucleic acids are well known in the art (see, e.g., Berger and Kimmel, 1987, Methods In Enzymology, Vol. 152: Guide To Molecular Cloning Techniques, San Diego: Academic Press, Inc. and Sambrook et al., 1989, Molecular Cloning: A Laboratory Manual, 2nd Ed., Vols. 1-3, Cold Spring Harbor Laboratory). Typically, stringent hybridization conditions for probes greater than 50 nucleotides are salt concentrations less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion at pH 7.0 to 8.3, and temperatures at least about 50° C., preferably at least about 60° C. As noted, stringent conditions may also be achieved with the addition of destabilizing agents such as formamide, in which case lower temperatures may be employed. Exemplary conditions include hybridization at 7% sodium dodecyl sulfate (SDS), 0.5 M NaPO₄ pH 7.0, 1 mM EDTA at 50° C. (or alternatively 65° C.); wash with 2×SSC, 1% SDS, at 50° C. (or alternatively 0.1-0.2 ×SSC, 1% SDS, at 50° C. or 65° C.). Other exemplary conditions for hybridization include (1) high stringency: 0.1×SSPE, 0.1% SDS, 65° C.; (2) medium stringency: 0.2×SSPE, 0.1% SDS, 50° C.; and (3) low stringency: 1.0×SSPE, 0.1% SDS, 50° C. Equivalent stringencies may be achieved using alternative buffers, salts and temperatures.

[0036] Alternatively, substantial sequence identity can be described as a percentage identity between two nucleotide or amino acid sequences. Two nucleic acid sequences are considered substantially identical when they are at least about 70% identical, at least about 75% identical, or at least about 80% identical, or at least about 85% identical, or at least about 90% identical, or at least about 95% or 98% identical. Two amino acid sequences are considered substantially identical when they are at least about 60%, sequence identical, more often at least about 70%, at least about 80%, or at least about 90% sequence identity to the reference sequence. Percentage sequence (nucleotide or amino acid) identity is typically calculated using art known means to determine the optimal alignment between two sequences and comparing the two sequences. Optimal alignment of sequences may be conducted using the local homology algorithm of Smith and Waterman (1981) Adv. Appl. Math. 2: 482, by the homology alignment algorithm of Needleman and Wunsch (1970) J. Mol. Biol. 48: 443, by the search for similarity method of Pearson and Lipman (1988) Proc. Natl. Acad. Sci. U.S.A. 85: 2444, by the BLAST algorithm of Altschul (1990) J. Mol. Biol. 215: 403-410; and Shpaer (1996) Genomics 38:179-191, or by the Needleham et al. (1970) J. Mol. Biol. 48: 443-453; and Sankoff et al., 1983, Time Warps, String Edits, and Macromolecules, The Theory and Practice of Sequence Comparison, Chapter One, Addison-Wesley, Reading, Mass.; generally by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.; BLAST from the National Center for Biotechnology Information (http:// www.ncbi.nlm.nih.gov/). In each case default parameters are used (for example the BLAST program uses as defaults a wordlength (W) of 11, the BLOSUM62 scoring matrix (see Henikoff (1992) Proc. Natl. Acad. Sci. USA 89: 10915-10919) alignments (B) of 50, expectation (E) of 10, M=5, N=−4, and a comparison of both strands).

[0037] As used herein the term “recombinant” has its usual meaning in the art and refers to a polynucleotide synthesized or otherwise manipulated in vitro, or to methods of using recombinant polynucleotides to produce gene products in cells or other biological systems. Thus, a “recombinant” polynucleotide is defined either by its method of production or its structure. In reference to its method of production, the process is use of recombinant nucleic acid techniques, e.g., involving human intervention in the nucleotide sequence, typically selection or production. Alternatively, a recombinant polynucleotide can be a polynucleotide made by generating a sequence comprising fusion of two fragments which are not naturally contiguous to each other, but is meant to exclude products of nature. Thus, for example, products made by transforming cells with any non-naturally occurring vector is encompassed, as are polynucleotides comprising sequence derived using any synthetic oligonucleotide process, as are polynucleotides from which a region has been deleted. A recombinant polynucleotide can also be a coding sequence that has been modified in vivo using a recombinant oligo or polynucleotide (such as a PKS in which a domain is inactivated by homologous recombination using a recombinant polynucleotide). A “recombinant” polypeptide is one expressed from a recombinant polynucleotide.

[0038] It will be immediately recognized by those of skill that recombinant polypeptides of the invention have a variety of uses, some of which are described in detail below, including but not limited to use as enzymes, or componants of enzymes, useful for the synthesis or modification of polyketides. Recombinant polypeptides encoded by the chalcomycin PKS gene cluster are also useful as antigens for production of antibodies. Such antibodies find use for purification of bacterial (e.g., Streptomyces bikiniensis) proteins, detection and typing of bacteria, and particularly, as tools for strain improvement (e.g., to assay PKS protein levels to identify “up-regulated” strains in which levels of polyketide producing or modifying proteins are elevated) or assessment of efficiency of expression of recombinant proteins. Polyclonal and monoclonal antibodies can be made by well known and routine methods (see, e.g., Harlow and Lane, 1988, ANTIBODIES: A LABORATORY MANUAL, COLD SPRING HARBOR LABORATORY, New York; Koehler and Milstein 1075, Nature 256:495). In selecting polypeptide sequences for antibody induction, it is not to retain biological activity; however, the protein fragment must be immunogenic, and preferably antigenic (as can be determined by routine methods). Generally the protein fragment is produced by recombinant expression of a DNA comprising at least about 60, more often at least about 200, or even at least about 500 or more base pairs of protein coding sequence, such as a polypeptide, module or domain derived from a chalcomycin polyketide synthase (PKS) gene cluster. Methods for expression of recombinant proteins are well known. (See, e.g., Ausubel et al., 2002, Current Protocols In Molecular Biology, Greene Publishing and Wiley-Interscience, New York.)

[0039] Further aspects of the invention include chimeric PKSs comprising a portion (in one embodiment at least a domain, optionally at least a module, or alternatively at least one polypeptide) from the chalcomycin PKS, and a portion (in one embodiment at least a domain, optionally at least a module, or alternatively at least a polypeptide) from one or more non-chalcomycin PKSs. For example, the invention provides (1) encoding DNA for a chimeric PKS that is substantially patterned on a non-chalcomycin producing enzyme, but which includes one or more functional domains or modules of chalcomycin PKS; (2) encoding DNA for a chimeric PKS that is substantially patterned on the chalcomycin PKS, but which includes one or more functional domains or modules of another PKS or NRPS; and (3) methods for making chalcomycin analogs and derivatives. With respect to item (1) above, examples include chimeric PKS enzymes wherein the genes for the erythromycin PKS, rapamycin PKS, tylosin PKS, and spiramycin PKS, or another PKS function as accepting genes, and one or more of the above-identified coding sequences for chalcomycin domains or modules are inserted as replacements for domains or modules of comparable function. With respect to item (2) above, examples include chimeric PKS enzymes wherein the chalcomycin PKS serves as an accepting gene, and genes for the erythromycin PKS, rapamycin PKS, tylosin PKS, and spiramycin PKS, or another PKS function as accepting genes, and one or more of the above-identified coding sequences for chalcomycin domains or modules are inserted as replacements for domains or modules of comparable function. A partial list of sources of PKS sequences for use in making chimeric molecules, for illustration and not limitation, includes Avermectin (U.S. Pat. No. 5,252,474; MacNeil et al., 1993, Industrial Microorganisms: Basic and Applied Molecular Genetics, Raltz. Hegeman, & Skatrud, eds. (ASM), pp. 245-256; MacNeil et al., 1992, Gene 115: 119-25); Candicidin (FRO008) (Hu et al., 1994, Mol. Microbiol. 14: 163-72); Epothilone (U.S. Pat. No. 6,303,342); Erythromycin (WO 93/13663; U.S. Pat. No. 5,824,513; Donadio et al., 1991, Science 252:675-79; Cortes et al., 1990, Nature 348:176-8); FK-506 (Motamedi et al., 1998, Eur. J. Biochem. 256:528-34; Motamedi et al., 1997, Eur. J. Biochem. 244:74-80); FK-520 (U.S. Pat. No. 6,503,737; see also Nielsen et al., 1991, Biochem. 30:5789-96); Lovastatin (U.S. Pat. No. 5,744,350); Nemadectin (MacNeil et al., 1993, supra); Niddamycin (Kakavas et al., 1997, J. Bacteriol. 179:7515-22); Oleandomycin (Swan et al., 1994, Mol. Gen. Genet. 242:358-62; U.S. Pat. No. 6,388,099; Olano et al., 1998, Mol. Gen. Genet. 259:299-308); Platenolide (EP Pat. App. 791,656 ); Rapamycin (Schwecke et al., 1995, Proc. Natl. Acad. Sci. USA 92:7839-43); Aparicio et al., 1996, Gene 169:9-16); Rifamycin (August et al., 1998, Chemistry & Biology, 5: 69-79); Soraphen (U.S. Pat. No. 5,716,849; Schupp et al., 1995, J. Bacteriology 177: 3673-79); Spiramycin (U.S. Pat. No. 5,098,837); Tylosin (EP 0 791,655; Kuhstoss et al., 1996, Gene 183:231-36; U.S. Pat. No. 5,876,991). Additional suitable PKS coding sequences remain to be discovered and characterized, but will be available to those of skill (e.g., by reference to GenBank).

[0040] Construction of such chimeric enzymes is most effectively achieved by construction of appropriate encoding polynucleotides. In preparing modified and chimeric proteins, it is not necessary, although it may be most efficient, to replace or substitute one or more entire domains or modules of one PKS (e.g., the chalcomycin PKS or another PKS) with an entire domain or module of a different PKS (e.g., the chalcomycin PKS or another PKS). Rather, peptide subsequences of a PKS domain or module that correspond to a peptide subsequence in an accepting domain or module, or which otherwise provide useful function, may be used as replacements. Accordingly, appropriate encoding DNAs for construction of such chimeric PKS include those that encode at least 10, 15, 20 or more amino acids of a selected chalcomycin domain or module. Recombinant methods for manipulating modular PKS genes to make chimeric PKS enzymes are described in U.S. Pat. Nos. 5,672,491; 5,843,718; 5,830,750; and 5,712,146; and in PCT publication Nos. 98/49315 and 97/02358. A number of genetic engineering strategies have been used with DEBS to demonstrate that the structures of polyketides can be manipulated to produce novel natural products, primarily analogs of the erythromycins (see the patent publications referenced supra and Hutchinson, 1998, Curr Opin Microbiol. 1:319-329, and Baltz, 1998, Trends Microbiol. 6:76-83).

[0041] The invention methods may be directed to the preparation of an individual polyketide. The polyketide may or may not be novel, but the method of preparation permits a more convenient or alternative method of preparing it. The resulting polyketides may be further modified to convert them to other useful compounds. Examples of chemical structures of sixteen-membered macrolides that can be made using the materials and methods of the present invention are described in PCT Patent Publication WO 02/32916; U.S. Patent Application US20020128213A (app. Ser. No. 09/969,177); and copending U.S. provisional patent application No. 60/493,966.

[0042] The recombinant DNAs and DNA vectors of the inventions can also be used to make “libraries” of polyketides. Generally, members of these polyketide libraries may themselves be novel compounds, and the invention further includes novel polyketide members of these libraries. Regardless of the naturally occurring PKS gene used as an acceptor, the invention provides libraries of polyketides by generating modifications in, or using a portion of, the chalcomycin PKS so that the protein complexes produced have altered activities in one or more respects, and thus produce polyketides other than the natural product of the PKS. Novel polyketides may thus be prepared, or polyketides in general prepared more readily, using this method. By providing a large number of different genes or gene clusters derived from a naturally occurring PKS gene cluster, each of which has been modified in a different way from the native cluster, an effectively combinatorial library of polyketides can be produced as a result of the multiple variations in these activities.

[0043] As noted, in one aspect the invention provides recombinant PKS wherein at least 10, 15, 20, or more consecutive amino acids in one or more domains of one or more modules thereof are derived from one or more domains of one or more modules of chalcomycin polyketide synthase. A polyketide synthase “derived from” a naturally occurring PKS contains the scaffolding encoded by all the portion employed of the naturally occurring synthase gene, contains at least two modules that are functional, and contains mutations, deletions, or replacements of one or more of the activities of these functional modules so that the nature of the resulting polyketide is altered. This definition applies both at the protein and genetic levels. Particular embodiments include those wherein a KS, AT, KR, DH, or ER has been deleted or replaced by a version of the activity from a different PKS or from another location within the same PKS, and derivatives where at least one noncondensation cycle enzymatic activity (KR, DH, or ER) has been deleted or wherein any of these activities has been added or mutated so as to change the ultimate polyketide synthesized.

[0044] There are at least five degrees of freedom for constructing a polyketide synthase in terms of the polyketide that will be produced. First, the polyketide chain length will be determined by the number of modules in the PKS. Second, the nature of the carbon skeleton of the PKS will be determined by the specificities of the acyl transferases which determine the nature of the extender units at each position—e.g., malonyl, methyl malonyl, methoxy malonyl, or ethyl malonyl, etc. Third, the loading domain specificity will also have an effect on the resulting carbon skeleton of the polyketide. Fourth, the oxidation state at various positions of the polyketide will be determined by the dehydratase and reductase portions of the modules. This will determine the presence and location of ketone, alcohol, alkene or alkane substituents at particular locations in the polyketide. Fifth, the stereochemistry of the resulting polyketide is a function of three aspects of the synthase. The first aspect is related to the AT/KS specificity associated with substituted malonyls as extender units, which affects stereochemistry only when the reductive cycle is missing or when it contains only a ketoreductase since the dehydratase would abolish chirality. Also, the specificity of the ketoreductase will determine the chirality of the corresponding hydroxyl group. Also, the enoyl reductase specificity for substituted malonyls as extender units will influence the result when there is a complete KR/DH/ER available.

[0045] As can be appreciated by those skilled in the art, polyketide biosynthesis can be manipulated to make a product other than the product of a naturally occurring PKS biosynthetic cluster. For example, AT domains can be altered or replaced to change specificity. For example, and not limitation, the AT domain of chalcomycin module 0 (loading domain) can be replaced by an AT with specificity for methylmalonyl-CoA to produce chalcomycin derivatives with a C-15 ethyl group in place of the C-15 methyl group. The variable domains within a module can be deleted and or inactivated or replaced with other variable domains found in other modules of the same PKS or from another PKS. See e.g., Katz & McDaniel, Med Res Rev 19: 543-558 (1999) and WO 98/49315. Similarly, entire modules can be deleted and/or replaced with other modules from the same PKS or another PKS. See e.g., Gokhale et al., Science 284:482 (1999) and WO 00/47724. For example, and not limitation, 3-hydroxy derivatives of chalcomycin can be produced using a modified chalcomycin PKS in which module 7 of the chalcomycin PKS is replaced by module 7 of the tylosin PKS (optionally with appropriate linker modifications). Similarly, protein subunits of different PKSs also can be mixed and matched to make compounds having the desired backbone and modifications. For example, subunits of 1 and 2 (encoding modules 1-4) of the pikromycin PKS were combined with the DEBS3 subunit to make a hybrid PKS product (see Tang et al., Science, 287: 640 (2001), WO 00/26349 and WO 99/6159). Also see Examples, below.

[0046] Mutations can be introduced into PKS genes such that polypeptides with altered activity are encoded. Polypeptides with “altered activity” include those in which one or more domains are inactivated or deleted, or in which a mutation changes the substrate specificity of a domain, as well as other alterations in activity. Mutations can be made to the native sequences using conventional techniques. The substrates for mutation can be an entire cluster of genes or only one or two of them; the substrate for mutation may also be portions of one or more of these genes. Techniques for mutation include preparing synthetic oligonucleotides including the mutations and inserting the mutated sequence into the gene encoding a PKS subunit using restriction endonuclease digestion. (See, e.g., Kunkel, T. A. Proc Natl Acad Sci USA (1985) 82:448; Geisselsoder et al. BioTechniques (1987) 5:786.) Alternatively, the mutations can be effected using a mismatched primer (generally 10-20 nucleotides in length) that hybridizes to the native nucleotide sequence (generally cDNA corresponding to the RNA sequence), at a temperature below the melting temperature of the mismatched duplex. The primer can be made specific by keeping primer length and base composition within relatively narrow limits and by keeping the mutant base centrally located. (See Zoller and Smith, Methods in Enzymology (1983) 100:468). Primer extension is effected using DNA polymerase. The product of the extension reaction is cloned, and those clones containing the mutated DNA are selected. Selection can be accomplished using the mutant primer as a hybridization probe. The technique is also applicable for generating multiple point mutations. (See, e.g., Dalbie-McFarland et al. Proc Natl Acad Sci USA (1982) 79:6409). PCR mutagenesis can also be used for effecting the desired mutations.

[0047] Random mutagenesis of selected portions of the nucleotide sequences encoding enzymatic activities can be accomplished by several different techniques known in the art, e.g., by inserting an oligonucleotide linker randomly into a plasmid, by irradiation with X-rays or ultraviolet light, by incorporating incorrect nucleotides during in vitro DNA synthesis, by error-prone PCR mutagenesis, and by preparing synthetic mutants or by damaging plasmid DNA in vitro with chemicals. Chemical mutagens include, for example, sodium bisulfite, nitrous acid, hydroxylamine, agents which damage or remove bases thereby preventing normal base-pairing such as hydrazine or formic acid, analogues of nucleotide precursors such as nitrosoguanidine, 5-bromouracil, 2-aminopurine, or acridine intercalating agents such as proflavine, acriflavine, quinacrine, and the like. Generally, plasmid DNA or DNA fragments are treated with chemicals, transformed into E. coli and propagated as a pool or library of mutant plasmids.

[0048] In addition to providing mutated forms of regions encoding enzymatic activity, regions encoding corresponding activities from different PKS synthases or from different locations in the same PKS synthase can be recovered, for example, using PCR techniques with appropriate primers. By “corresponding” activity encoding regions is meant those regions encoding the same general type of activity—e.g., a ketoreductase activity in one location of a gene cluster would “correspond” to a ketoreductase-encoding activity in another location in the gene cluster or in a different gene cluster; similarly, a complete reductase cycle could be considered corresponding—e.g., KR/DH/ER could correspond to KR alone.

[0049] If replacement of a particular target region in a host polyketide synthase is to be made, this replacement can be conducted in vitro using suitable restriction enzymes or can be effected in vivo using recombinant techniques involving homologous sequences framing the replacement gene. One such system involving plasmids of differing temperature sensitivities is described in PCT application WO 96/40968. Another useful method for modifying a PKS gene (e.g., making domain substitutions or “swaps”) is a RED/ET cloning procedure developed for constructing domain swaps or modifications in an expression plasmid without first introducing restriction sites. The method is related to ET cloning methods (see, Datansko & Wanner, 2000, Proc. Natl. Acad. Sci. U.S.A. 97, 6640-45; Muyrers et al, 2000, Genetic Engineering 22:77-98). The RED/ET cloning procedure is used to introduce a unique restriction site in the recipient plasmid at the location of the targeted domain. This restriction site is used to subsequently linearize the recipient plasmid in a subsequent ET cloning step to introduce the modification. This linearization step is necessary in the absence of a selectable marker, which cannot be used for domain substitutions. An advantage of using this method for PKS engineering is that restriction sites do not have to be introduced in the recipient plasmid in order to construct the swap, which makes it faster and more powerful because boundary junctions can be altered more easily.

[0050] In one embodiment, the invention provides a chimeric PKS in which one of more polypeptides are derived from a chalcomycin PKS polypeptide, and one or more peptides are derived from one or more non-chalcomycin PKS(s) that, like the chalcomysin PKS, produces a 16-membered macrolide. Examples of PKS(s) that produces a 16-membered macrolide include, for example, the tylosin PKS, the spiramycin PKS, the niddamycin PKS, and the mycinamicin PKS. All the currently known PKSs for 16-membered macrolides consists of five large polypeptides encoded by colinear genes in a single operon. The arrangement of modules on these polypeptides is conserved. Thus, for known 16-membered macrolide PKSs, the first polypeptide has a loading module and two extender modules, the second a single extender module, the third two extender modules, the fourth a single extender module, and the fifth a single extender module followed by a thioesterase domain. The different aglycone core structures produced by different 16-membered macrolide PKSs is due to differences in the catalytic domains within each of these modules.

[0051] As is illustrated in the examples, below, new hybrid 16-membered macrolides can be made by expressing combinations of PKS polypeptides from different sources in a suitable host. The hybrid PKS produces hybrid polyketides that, optionally can be further modified by the post-PKS tailoring enzymes present within the host. See Examples, infra.

[0052] By expressing particular combinations of these PKS polypeptides one can produce molecules with desired combinations of structural features based on, for example, the macrolactone structural features specified by each of the five polypeptides of different 16-membered macrolide PKSs as shown in Table 1, below. As noted, by expressing particular combinations of these PKS polypeptides one can produce molecules with desired combinations of structural features. Although, as described in the Examples and Table 1, selection of particular combinations of polypeptides provides a level of predictability as to the products formed by the hybrid PKS, the invention is not limited to any particular combinations or structures “predicted” by the table. TABLE 1 PKS 1 2 3 4 5 TylG 15-ethyl 10,11-ene 9-keto 5-hydroxy 3-hydroxy 14-methyl 10-H 8-methyl 4-methyl 2-H 12,13-ene 7-methylene 12-methyl 6-ethyl SrmG 15-methyl 10,11-ene 9-keto 5-hydroxy 3-hydroxy 14-H 10-H 8-methyl 4-methoxy 2-H 12,13-ene 7-methylene 12-H 6-ethyl ChmG 15-methyl 10,11-ene 9-keto 5-hydroxy 3-keto 14-methyl 10-H 8-methyl 4-methyl 2-H 12,13-ene 7-methylene 12-H 6-methyl

[0053] In one embodiment, the components of the chimeric PKS are arranged onto polypeptides having interpolypeptide linkers that direct the assembly of the polypeptides into the functional PKS protein, such that it is not required that the PKS have the same arrangement of modules in the polypeptides as observed in natural PKSs. Suitable interpolypeptide linkers to join polypeptides and intrapolypeptide linkers to join modules within a polypeptide are described in PCT publication WO 00/47724.

[0054] In one embodiment of the invention, the components of the PKS are arranged into five polypeptides similarly to natural PKS proteins involved in the biosynthesis of tylactone, platenolide, and the like. Thus, for example, the first polypeptide comprises the loading domain, first and second extender modules, and a C-terminal interpolypeptide linker region suitable for interaction with the second polypeptide. The second polypeptide comprises an N-terminal interpolypeptide linker region suitable for interaction with the first polypeptide, the third extender module, and a C-terminal interpolypeptide linker region suitable for interaction with the third polypeptide. The third polypeptide comprises an N-terminal interpolypeptide linker region suitable for interaction with the second polypeptide, the fourth and fifth extender modules, and a C-terminal interpolypeptide linker region suitable for interaction with the fourth polypeptide. The fourth polypeptide comprises an N-terminal interpolypeptide linker region suitable for interaction with the third polypeptide, the sixth extender module, and a C-terminal interpolypeptide linker region suitable for interaction with the fifth polypeptide. The fifth polypeptide comprises an N-terminal interpolypeptide linker region suitable for interaction with the fourth polypeptide, the seventh extender module, and the terminal thioesterase domain.

[0055] In other embodiments of the invention, the components of the PKS residing on any given polypeptide are derived from the same source, and are naturally contiguous in that source, but the intrapolypeptide linkers are changed to allow proper assembly across heterologous polypeptide junctions to form a functional PKS. For example, in one embodiment of the invention, the first polypeptide is the intact first polypeptide of the chalcomycin PKS, encoded by chmGI, and comprises the loading domain and first and second extender modules from the chalcomycin PKS together with the native C-terminal interpolypeptide linker region that directs interaction of the first polypeptide with the second polypeptide of the chalcomycin PKS. The second polypeptide comprises the N-terminal interpolypeptide linker and module 3 of the chalcomycin PKS, encoded by chmGII, but with the C-terminal interpolypeptide linker replaced by the C-terminal interpolypeptide linker from the second polypeptide of the spiramycin PKS, encoded by srmG2. This replaced C-terminal interpolypeptide linker directs the second polypeptide to interact with the third polypeptide, taken from the spiramycin PKS and encoded by the srmG3 gene. The remaining polypeptides are the third, fourth, and fifth polypeptides of the spiramycin PKS, encoded by srmG3, srmG4, and srmG5, respectively. In another embodiment of the invention, the first polypeptide comprises the loading domain and first, second and third extender modules from the chalcomycin PKS, together with a C-terminal interpolypeptide linker region derived from the C-terminus of the first polypeptide of the tylosin PKS. The remaining polypeptides are the third, fourth, and fifth polypeptides of the tylosin PKS. The use of the appropriate interpolypeptide linkers directs the proper assembly of the PKS, thereby improving the catalytic activity of the resulting hybrid PKS.

[0056] As noted above, the DNA compounds of the invention can be expressed in host cells for production of known and novel compounds. Preferred hosts include fungal systems such as yeast and procaryotic hosts, but single cell cultures of, for example, mammalian cells could also be used. A variety of methods for heterologous expression of PKS genes and host cells suitable for expression of these genes and production of polyketides are described, for example, in U.S. Pat. Nos. 5,843,718 and 5,830,750; WO 01/31035, WO 01/27306, and WO 02/068613; and U.S. patent application Ser. Nos. 10/087,451 (published as US2002000087451); 60/355,211; and 60/396,513 (corresponding to published application 20020045220).

[0057] Appropriate host cells for the expression of the hybrid PKS genes include those organisms capable of producing the needed precursors, such as malonyl-CoA, methylmalonyl-CoA, ethylmalonyl-CoA, and methoxymalonyl-ACP, and having phosphopantotheinylation systems capable of activating the ACP domains of modular PKSs. See, for example, U.S. Pat. No. 6,579,695. However, as disclosed in U.S. Pat. No. 6,033,883, a wide variety of hosts can be used, even tnough some hosts natively do not contain the appropriate post-translational mechanisms to activate the acyl carrier proteins of the synthases. Also see WO 97/13845 and WO 98/27203. The host cell may natively produce none, some, or all of the required polyketide precursors, and may be genetically engineered so as to produce the required polyketide precursors. Such hosts can be modified with the appropriate recombinant enzymes to effect these modifications. Suitable host cells include Streptomyces, E. coli, yeast, and other procaryotic hosts which use control sequences compatible with Streptomyces spp. Examples of suitable hosts that either natively produce modular polyketides or have been engineered so as to produce modular polyketides include but are not limited to actinomycetes such as Streptomyces coelicolor, Streptomyces venezuelae, Streptomyces fradiae, Streptomyces ambofaciens, and Saccharopolyspora erythraea, eubacteria such as Escherichia coli, myxobacteria such as Myxococcus xanthus, and yeasts such as Saccharomyces cerevisiae.

[0058] In one embodiment, any native modular PKS genes in the host cell have been deleted to produce a “clean host,” as described in U.S. Pat. No. 5,672,491, incorporated herein by reference. The construction of the clean host S. fradiae K159-1, and the clean host S. fradiae K159-1/244-17a that produces methoxymalonyl-ACP are described below in Examples 2 and 3. Other organisms can be engineered using similar methods.

[0059] In some embodiments, the host cell expresses, or is engineered to express, a polyketide “tailoring” or “modifying” enzyme. Once a PKS product is released, it is subject to post-PKS tailoring reactions. These reactions are important for biological activity and for the diversity seen among 16-membered macrolides. Tailoring enzymes normally associated with polyketide biosynthesis include oxygenases, glycosyl- and methyltransferases, acyltransferases, halogenases, cyclases, aminotransferases, and hydroxylases. Tailoring enzymes for modification of a product of the chalcomycin PKS, a non-chalcomycin PKS, or a chimeric PKS, can be those normally associated with chalcomycin biosynthesis (including, but not limited to, proteins described in Table 2) or “heterologous” tailoring enzymes. As noted above, the P450 hydrolases encoded by the chmHI, chmPI and chmPII genes are of particular interest for production of polyketides having hydroxy groups well suited for subsequent chemical modification.

[0060] For purposes of the present invention, tailoring enzymes can be expressed in the organism in which they are naturally produced, or as recombinant proteins in heterologous hosts. For example, as shown in Examples 6 and 7, a hybrid PKSs having elements from the chalcomycin and spiramycin PKSs, or from the tylosin and chalcomysin PKSs were expressed in an engineered host derived from a tylosin producing strain of S. fradiae in which all or most of the post-PKS tailoring reactions of the tylosin biosynthetic pathway (see Baltz and Seno, 1988, “Genetics of Streptomyces fradiae and tylosin biosynthesis” Annu Rev Microbiol. 42:547-74) were expressed and which modified the polyketide product.

[0061] In some cases, the structure produced by the heterologous or hybrid PKS may be modified with different efficiencies by post-PKS tailoring enzymes from different sources. In such cases, post-PKS tailoring enzymes can be recruited from other pathways to obtain the desired compound. For example, as discussed in Example 6, a chmH gene has been used to modify the product of a chalcomycin-spiramycin hybrid PKS. Similarly, host cells can be selected, or engineered, for expression of a glycosylatation apparatus (discussed below), amide synthases, (see, for example, U.S. patent publication 20020045220 “Biosynthesis of Polyketide Synthase Substrates”). For example and not limitation, the host cell can contain the desosamine, megosamine, and/or mycarose biosynthetic genes, corresponding glycosyl transferase genes, and hydroxylase genes (e.g., picK, megK, eryK, megF, and/or eryF). Methods for glycosylating polyketides are generally known in the art and can be applied in accordance with the methods of the present invention; the glycosylation may be effected intracellularly by providing the appropriate glycosylation enzymes or may be effected in vitro using chemical synthetic means as described herein and in WO 98/49315, incorporated herein by reference. Glycosylation with desosamine, mycarose, and/or megosamine is effected in accordance with the methods of the invention in recombinant host cells provided by the invention. Alternatively and as noted, glycosylation may be effected intracellularly using endogenous or recombinantly produced intracellular glycosylases. In addition, synthetic chemical methods may be employed.

[0062] Alternatively, the aglycone compounds can be produced in the recombinant host cell, and the desired modification (e.g., glycosylation and hydroxylation) steps carried out in vitro (e.g., using purified enzymes, isolated from native sources or recombinantly produced) or in vivo in a converting cell different from the host cell (e.g., by supplying the converting cell with the aglycone).

[0063] It will be apparent to the reader that a variety of recombinant vectors can be utilized in the practice of aspects of the invention. As used herein, “vector” refers to polynucleotide elements that are used to introduce recombinant nucleic acid into cells for either expression or replication. Selection and use of such vehicles is routine in the art. An “expression vector” includes vectors capable of expressing DNAs that are operatively linked with regulatory sequences, such as promoter regions. Thus, an expression vector refers to a recombinant DNA or RNA construct, such as a plasmid, a phage, recombinant virus or other vector that, upon introduction into an appropriate host cell, results in expression of the cloned DNA. Appropriate expression vectors are well known to those of skill in the art and include those that are replicable in eukaryotic cells and/or prokaryotic cells and those that remain episomal or those which integrate into the host cell genome.

[0064] The vectors used to perform the various operations to replace the enzymatic activity in the host PKS genes or to support mutations in these regions of the host PKS genes may be chosen to contain control sequences operably linked to the resulting coding sequences in a manner that expression of the coding sequences may be effected in an appropriate host. Suitable control sequences include those which function in eucaryotic and procaryotic host cells. If the cloning vectors employed to obtain PKS genes encoding derived PKS lack control sequences for expression operably linked to the encoding nucleotide sequences, the nucleotide sequences are inserted into appropriate expression vectors. This can be done individually, or using a pool of isolated encoding nucleotide sequences, which can be inserted into host vectors, the resulting vectors transformed or transfected into host cells, and the resulting cells plated out into individual colonies.

[0065] Suitable control sequences for single cell cultures of various types of organisms are well known in the art. Control systems for expression in yeast are widely available and are routinely used. Control elements include promoters, optionally containing operator sequences, and other elements depending on the nature of the host, such as ribosome binding sites. Particularly useful promoters for procaryotic hosts include those from PKS gene clusters which result in the production of polyketides as secondary metabolites, including those from Type I or aromatic (Type II) PKS gene clusters. Examples are act promoters, tcm promoters, spiramycin promoters, tylosin promoter (e.g., tylGIp, see Rodriguez et al., “Rapid engineering of polyketide overproduction by gene transfer to industrially optimized strains” J Ind Microbiol Biotechnol. Apr. 16, 2003; and DeHoff et al., “Streptomyces fradiae tylactone synthase, starter module and modules 1-7, (tylG) gene, complete cds” Genbank Accession No. U78289), and other promoters. However, other bacterial promoters, such as those derived from sugar metabolizing enzymes, such as galactose, lactose (lac) and maltose, are also useful. Additional examples include promoters derived from biosynthetic enzymes such as for tryptophan (trp), the β-lactamase (bla), bacteriophage lambda PL, and T5. In addition, synthetic promoters, such as the tac promoter (U.S. Pat. No. 4,551,433), can be used.

[0066] As noted, particularly useful control sequences are those which themselves, or with suitable regulatory systems, activate expression during transition from growth to stationary phase in the vegetative mycelium. The system contained in the plasmid identified as pCK7, i.e., the actI/actIII promoter pair and the actII-ORF4 (an activator gene), is particularly preferred. Particularly preferred hosts are those which lack their own means for producing polyketides so that a cleaner result is obtained. Illustrative control sequences, vectors, and host cells of these types include the modified S. coelicolor CH999 and vectors described in PCT publication WO 96/40968 and similar strains of S. lividans. See U.S. Pat. Nos. 5,672,491; 5,830,750, 5,843,718; and 6,177,262, each of which is incorporated herein by reference.

[0067] Other regulatory sequences may also be desirable which allow for regulation of expression of the PKS sequences relative to the growth of the host cell. Regulatory sequences are known to those of skill in the art, and examples include those which cause the expression of a gene to be turned on or off in response to a chemical or physical stimulus, including the presence of a regulatory compound. Other types of regulatory elements may also be present in the vector, for example, enhancer sequences.

[0068] Selectable markers can also be included in the recombinant expression vectors. A variety of markers are known which are useful in selecting for transformed cell lines and generally comprise a gene whose expression confers a selectable phenotype on transformed cells when the cells are grown in an appropriate selective medium. Such markers include, for example, genes which confer antibiotic resistance or sensitivity to the plasmid. Alternatively, several polyketides are naturally colored, and this characteristic provides a built-in marker for screening cells successfully transformed by the present constructs.

[0069] The various PKS nucleotide sequences, or a mixture of such sequences, can be cloned into one or more recombinant vectors as individual cassettes, with separate control elements or under the control of a single promoter. The PKS subunits or components can include flanking restriction sites to allow for the easy deletion and insertion of other PKS subunits so that hybrid or chimeric PKSs can be generated. The design of such restriction sites is known to those of skill in the art and can be accomplished using the techniques described above, such as site-directed mutagenesis and PCR. Methods for introducing the recombinant vectors of the present invention into suitable hosts are known to those of skill in the art and typically include the use of CaCl₂ or other agents, such as divalent cations, lipofection, DMSO, protoplast transformation, conjugation, and electroporation.

[0070] Expression vectors containing nucleotide sequences encoding a variety of PKS systems for the production of different polyketides can be transformed into the appropriate host cells to construct a polyketide library. In one approach, a mixture of such vectors is transformed into the selected host cells and the resulting cells plated into individual colonies and selected for successful transformants. Each individual colony has the ability to produce a particular PKS and ultimately a particular polyketide. Typically, there will be duplications in some of the colonies; the subset of the transformed colonies that contains a different PKS in each member colony can be considered the library. Alternatively, the expression vectors can be used individually to transform hosts, which transformed hosts are then assembled into a library. A variety of strategies might be devised to obtain a multiplicity of colonies each containing a PKS gene cluster derived from the naturally occurring host gene cluster so that each colony in the library produces a different PKS and ultimately a different polyketide. The number of different polyketides that are produced by the library is typically at least four, more typically at least ten, and preferably at least 20, more preferably at least 50, reflecting similar numbers of different altered PKS gene clusters and PKS gene products. The number of members in the library is arbitrarily chosen; however, the degrees of freedom outlined above with respect to the variation of starter, extender units, stereochemistry, oxidation state, and chain length is quite large. The polyketide producing colonies can be identified and isolated using known techniques and the produced polyketides further characterized. The polyketides produced by these colonies can be used collectively in a panel to represent a library or may be assessed individually for activity.

[0071] The libraries can thus be considered at four levels: (1) a multiplicity of colonies each with a different PKS encoding sequence encoding a different PKS cluster but all derived from a naturally occurring PKS cluster; (2) colonies which contain the proteins that are members of the PKS produced by the coding sequences; (3) the polyketides produced; and (4) compounds derived from the polyketides. Of course, combination libraries can also be constructed wherein members of a library derived, for example, from the erythromycin PKS can be considered as a part of the same library as those derived from, for example, the rapamycin PKS cluster.

[0072] Colonies in the library are induced to produce the relevant synthases and thus to produce the relevant polyketides to obtain a library of candidate polyketides. The polyketides secreted into the media can be screened for binding to desired targets, such as receptors, signaling proteins, and the like. The supernatants per se can be used for screening, or partial or complete purification of the polyketides can first be effected. Typically, such screening methods involve detecting the binding of each member of the library to receptor or other target ligand. Binding can be detected either directly or through a competition assay. Means to screen such libraries for binding are well known in the art. Alternatively, individual polyketide members of the library can be tested against a desired target. In this event, screens wherein the biological response of the target is measured can be included.

[0073] Thus, the present invention provides recombinant DNA molecules and vectors comprising those recombinant DNA molecules that encode all or a portion of the chalcomycin PKS and/or chalcomycin modification enzymes and that, when transformed into a host cell and the host cell is cultured under conditions that lead to the expression of said chalcomycin PKS and/or modification enzymes, results in the production of polyketides including but not limited to chalcomycin and/or analogs or derivatives thereof in useful quantities. The present invention also provides recombinant host cells comprising those recombinant vectors.

[0074] Suitable culture conditions for production of polyketides using the cells of the invention will vary according to the host cell and the nature of the polyketide being produced, but will be know to those of skill in the art. See, for example, the examples below and WO 98/27203 “Production of Polyketides in Bacteria and Yeast” and WO 01/83803 “Overproduction Hosts for Biosynthesis of Polyketides.”

[0075] The polyketide product produced by host cells of the invention can be recovered (i.e., separated from the producing cells and at least partially purified) using routine techniques (e.g., extraction from broth followed by chromatography).

[0076] The compositions, cells and methods of the invention may be directed to the preparation of an individual polyketide or a number of polyketides. The polyketide may or may not be novel, but the method of preparation permits a more convenient or alternative method of preparing it. It will be understood that the resulting polyketides may be further modified to convert them to other useful compounds. For example, an ester linkage may be added to produce a “pharmaceutically acceptable ester” (i.e., an ester that hydrolyzes under physiologically relevant conditions to produce a compound or a salt thereof). Illustrative examples of suitable ester groups include but are not limited to formates, acetates, propionates, butyrates, succinates, and ethylsuccinates.

[0077] The polyketide product produced by recombinant cells can be chemically modified in a variety of ways. For example , for example by addition of a protecting group, for example to produce prodrug forms. A variety of protecting groups are disclosed, for example, in T. H. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, Third Edition, John Wiley & Sons, New York (1999). Prodrugs are in general functional derivatives of the compounds that are readily convertible in vivo into the required compound. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in “Design of Prodrugs,” H. Bundgaard ed., Elsevier, 1985.

[0078] Similarly, improvements in water solubility of a polyketide compound can be achieved by addition of groups containing solubilizing functionalities to the compound or by removal of hydrophobic groups from the compound, so as to decrease the lipophilicity of the compound. Typical groups containing solubilizing functionalities include, but are not limited to: 2-(dimethylaminoethyl)amino, piperidinyl, N-alkylpiperidinyl, hexahydropyranyl, furfuryl, tetrahydro furfuryl, pyrrolidinyl, N-alkylpyrrolidinyl, piperazinylamino, N-alkylpiperazinyl, morpholinyl, N-alkylaziridinylmethyl, (1-azabicyclo[1.3.0]hex-1-yl)ethyl, 2-(N-methylpyrrolidin-2-yl) ethyl, 2-(4-imidazolyl)ethyl, 2-(1-methyl-4-imidazolyl)ethyl, 2-(1-methyl-5-imidazolyl)ethyl, 2-(4-pyridyl)ethyl, and 3-(4-morpholino)-1-propyl. In the case of geldanamycin analogs, solubilizing groups can be added by reaction with amines, which results in the displacement of the 17-methoxy group by the amine (see, Schnur et al., 1995, “Inhibition of the Oncogene Product p185^(erbB-2) in Vitro and in Vivo by Geldanamycin and Dihydrogeldanamycin Derivatives,”, J. Med. Chem. 38, 3806-3812; Schnur et al., 1995 “erbB-2 Oncogene Inhibition by Geldanamycin Derivatives: Synthesis, Mechanism of Action, and Structure-Activity relationships,” J. Med. Chem. 38, 3813-3820; Schnur et al., “Ansamycin Derivatives as Antioncogene and Anticancer Agents,” U.S. Pat. No. 5,932,655; all of which are incorporated herein by reference). Typical amines containing solubilizing functionalities include 2-(dimethylamino)-ethylamine, 4-aminopiperidine, 4-amino-1-methylpiperidine, 4-aminohexahydropyran, furfurylamine, tetrahydrofurfurylamine, 3-(aminomethyl)-tetrahydrofuran, 2-(amino-methyl)pyrrolidone, 2-(aminomethyl)-1-methylpyrrolidine, 1-methylpiperazine, morpholine, 1-methyl-2(aminomethyl)aziridine, 1-(2-aminoethyl)-1-azabicyclo-[1.3.0]hexane, 1-(2-aminoethyl)piperazine, 4-(2-aminoethyl)morpholine, 1-(2-amino-ethyl) pyrrolidine, 2-(2-aminoethyl)pyridine, 2-fluoroethylamine, 2,2-difluoroethylamine, and the like.

[0079] In addition to post synthesis chemical or biosynthetic modifications, various polyketide forms or compositions can be produced, including but not limited to mixtures of polyketides, enantiomers, diastereomers, geometrical isomers, polymorphic crystalline forms and solvates, and combinations and mixtures thereof can be produced

[0080] Many other modifications of polyketides produced according to the invention will be apparent to those of skill, and can be accomplished using techniques of pharmaceutical chemistry.

[0081] Prior to use the PKS product (whether modified or not) can be formulated for storage, stability or administration. For example, the polyketide products can be formulated as a “pharmaceutically acceptable salt.” Suitable pharmaceutically acceptable salts of compounds include acid addition salts which may, for example, be formed by mixing a solution of the compound with a solution of a pharmaceutically acceptable acid such as hydrochloric acid, hydrobromic acid, sulfuric acid, fumaric acid, maleic acid, succinic acid, benzoic acid, acetic acid, citric acid, tartaric acid, phosphoric acid, carbonic acid, or the like. Where the compounds carry one or more acidic moieties, pharmaceutically acceptable salts may be formed by treatment of a solution of the compound with a solution of a pharmaceutically acceptable base, such as lithium hydroxide, sodium hydroxide, potassium hydroxide, tetraalkylammonium hydroxide, lithium carbonate, sodium carbonate, potassium carbonate, ammonia, alkylamines, or the like.

[0082] Prior to administration to a mammal the PKS product will be formulated as a pharmaceutical composition according to methods well known in the art, e.g., combination with a pharmaceutically acceptable carrier. The term “pharmaceutically acceptable carrier” refers to a medium that is used to prepare a desired dosage form of a compound. A pharmaceutically acceptable carrier can include one or more solvents, diluents, or other liquid vehicles; dispersion or suspension aids; surface active agents; isotonic agents; thickening or emulsifying agents; preservatives; solid binders; lubricants; and the like. Remington's Pharmaceutical Sciences, Fifteenth Edition, E. W. Martin (Mack Publishing Co., Easton, Pa., 1975) and Handbook of Pharmaceutical Excipients, Third Edition, A. H. Kibbe ed. (American Pharmaceutical Assoc. 2000), disclose various carriers used in formulating pharmaceutical compositions and known techniques for the preparation thereof.

[0083] The composition may be administered in any suitable form such as solid, semisolid, or liquid form. See Pharmaceutical Dosage Forms and Drug Delivery Systems, 5^(th) edition, Lippicott Williams & Wilkins (1991). In an embodiment, for illustration and not limitation, the polyketide is combined in admixture with an organic or inorganic carrier or excipient suitable for external, enteral, or parenteral application. The active ingredient may be compounded, for example, with the usual non-toxic, pharmaceutically acceptable carriers for tablets, pellets, capsules, suppositories, pessaries, solutions, emulsions, suspensions, and any other form suitable for use. The carriers that can be used include water, glucose, lactose, gum acacia, gelatin, mannitol, starch paste, magnesium trisilicate, talc, corn starch, keratin, colloidal silica, potato starch, urea, and other carriers suitable for use in manufacturing preparations, in solid, semi-solid, or liquified form. In addition, auxiliary stabilizing, thickening, and coloring agents and perfumes may be used.

[0084] It will be apparent from the forgoing that the invention provides may useful compositions and methods of using them. Without intending to limit its scope, in one aspect, the invention provides a recombinant DNA molecule that encodes a polypeptide, module or domain derived from a chalcomycin polyketide synthase (PKS) gene cluster. In an embodiment, the DNA molecule (or its complement) has substantial sequence identity to SEQ ID NO:1. In an embodiment, the DNA molecule hybridizes under stringent conditions to a nucleic acid having the sequence of SEQ ID NO:1 or its complement. In a related aspect, the invention provides a recombinant DNA molecule, comprising a sequence of at least about 200, optionally at least about 500, basepairs with a sequence identical or substantially identical to a protein encoding region of SEQ ID NO:1. In an embodiment, the DNA molecule encodes a polypeptide, module or domain derived from a chalcomycin polyketide synthase (PKS) gene cluster.

[0085] In one embodiment, the recombinant DNA molecule comprises a sequence encoding at least one module of a chalcomycin polyketide synthase. In an embodiment, the recombinant DNA molecule encodes a chalcomycin polyketide synthase polypeptide selected from the group consisting of ChmGI, ChmGII, ChmGIII, ChmGIV, and ChmV.

[0086] In one aspect, the recombinant DNA molecule includes a coding sequence for a chalcomycin modifying enzyme, such as a chalcomycin P450 hydrolase enzyme selected from the group consisting of ChmHI, ChmPI, and ChmPII.

[0087] The invention also provides vector that comprise the recombinant DNA molecules of the invention. In an aspect, the invention provides a recombinant host cell comprising the vector. In a related aspect, the invention provides a recombinant host cell comprising a DNA molecule of the invention integrated into the cell chromosomal DNA.

[0088] Also provided is a chimeric PKS that comprises at least one domain of a chalcomycin PKS, and a cell containing such a chimeric PKS. In a related aspect, the invention provides a modified functional chalcomycin PKS that differs from the S. bikiniensis chalcomycin PKS by the inactivation of at least one domain of the chalcomycin PKS and/or addition of at least one domain of a non-chalcomycin PKS (for example, a loading domain, a thioesterase domain, an AT domain, a KS domain, an ACP domain, a KR domain, a DH domain, and an ER domain). The invention provides a cell comprising a modified functional PKS. The invention also provides a method to prepare an chalcomycin derivative which method comprises providing substrates including extender units to the cell.

[0089] In an aspect, the invention provides a recombinant expression system capable of producing a chalcomycin synthase domain in a host cell, said system comprising an encoding sequence for a chalcomycin polyketide synthase domain, and said encoding sequence being operably linked to control sequences effective in said cell to produce RNA that is translated into said domain, and a host cell modified to contain the recombinant expression system.

[0090] The invention provides an isolated polypeptide encoded by a recombinant chalcomycin polyketide synthase (PKS) gene, and a recombinant host cell containing or expressing such a polypeptide.

[0091] The invention also provides a recombinant S. bikiniensis cell in which a chmGI, chmGII, chmGIII, chmGIV, or chmV is disrupted so as to reduce or eliminate production of chalcomycin.

[0092] The invention also provides a recombinant DNA molecule encoding a first protein comprising one or more modules of a chalcomycin PKS and a second protein comprising one or more modules of a tylosin PKS or spiramycin PKS, optionally one or more polypeptides of a chalcomycin PKS and one or more polypeptides of a tylosin PKS or spiramycin PKS. In a related aspect, the invention provides a recombinant host cell comprising a hybrid polyketide synthase comprising one or more modules of a chalcomycin PKS and one or more modules of a tylosin PKS or spiramycin PKS.

EXAMPLES

[0093] The following examples are provided to illustrate, but are not intended to limit, the present invention.

Example 1 Isolation and Characterization of Chalcomycin PKS Cluster From Streptomyces bikiniensis NRRL 2737

[0094] Growth of organism and extraction of genomic DNA. For genomic DNA extraction, a spore stock of Streptomyces bikiniensis NRRL 2737 was used to prepare a seed culture. Spores were stored as a suspension in 25% (v/v) glycerol at −80° C. and used to inoculate 5 ml of unbuffered Trypticase Soy Broth (TSB) liquid media. The entire seed culture was transferred into 50 ml of the same growth medium in a 250 ml baffled Erlenmeyer flask and incubated with shaking for 24 h at 28° C. A 10 ml portion of the cell suspension was centrifuged (10,000×g) and the resulting pellet was washed once with 10 ml buffer 1 (Tris, 50 mM, pH7.5; 20 mM EDTA). The pellet was suspended in 3.5 ml of buffer 1 containing 150 μg/ml RNase (Sigma-Aldrich) and 1 mg/ml lysozyme. After incubation of the mixture at 37° C. for 30 min, the salt concentration was adjusted by adding 850 μl 5 M NaCl solution, then the mixture was extracted two times with phenol:chloroform:isoamylaclohol (25:24:1, vol/vol) with gentle agitation followed by centrifugation for 10 min at 3500×g. After precipitation with 1 vol of isopropanol, the genomic DNA knot was spooled on a glass rod and redissolved in 200 μl of water. This method yielded about 0.5 mg total DNA. Standard agarose gel electrophoresis using 0.7% Seakem® LE-Agarose (Bio Whiaker Molecular Applications, Rockland, Me.) at a voltage of 50 mV overnight revealed that the sample contained mainly high molecular weight DNA of 50 kb or greater.

[0095] PKS Probe design. Five degenerate PCR primers were designed (degKS1F 5′-TTCGAY SCSGVSTTCTTCGSAT-3′[SEQ ID NO:44]; degKS2F 5′-GCSATGGAYCCSCARCARCGSVT-3′[SEQ ID NO:45]; degKS3F 5′-SSCTSGTSGCSMTSCAYCWSGC-3′[SEQ ID NO:46]; degKS5R 5′-GTSCCSGTSCCRTGSSCYTCSAC-3′[SEQ ID NO:47]; degKS7R 5′-ASRTGSGCRTTSGTSCCSSWSA-3′[SEQ ID NO:48]) based on conserved regions of ketosynthase (KS) domains of type I PKS genes and codon bias of high G+C organisms. The primers were used in the following combinations: degKS1F/degKS5R, degKS2F/degKS5R and degKS3F/degKS7R. The PCR conditions for the amplification of KS domains were as follows: A total reaction volume of 50 μl contained 100 ng of S. bikiniensis total DNA, 200 pmol of each primer, 0.2 mM dNTP, 10% DMSO and 2.5 U Taq DNA polymerase (Roche Applied Science, Indianapolis, Ind.). Thirty-five cycles of PCR were performed using the following steps: denaturation (94° C.; 40 sec); annealing (55° C.; 30 sec); extension (72° C.; 60 sec), 35 cycles. The resulting PCR reactions were subjected to electrophoresis on 1% agarose gels and the PCR products of approximately 700 bp were extracted from the gels using the gel extraction kit from Quiagen (Valencia, Calif.) according to manufacturer's protocol. The fragments were treated with Pfu DNA Polymerase (Stratagene, La Jolla, Calif.) to remove the A overhangs and cloned into the plasmid vector pLitmus28 (New England Biolabs, Beverley, Mass.) cut with EcRV. Thirty-two “amplimers” (the ca. 700 bp PCR-amplified segment) for each primer pair were sequenced using standard protocols. Of the 96 inserts sequenced, 81 were found to be KS amplimers. Employing the sequence comparison program ClustalW, 15 of the 81 KS amplimers were found to be unique and were compared with the 8 KS sequences of the related tylosin PKS cluster of Streptomyces fradiae using the program ClustalW. Each KS amplimer was thus assigned to a particular KS within the putative chalcomycin PKS cluster.

[0096] Genomic library preparation. Approximately 10 μg of genomic DNA was partially digested with Sau3A1 (1 hr incubation using dilutions of the enzyme) and the digested DNA was run on an agarose gel with DNA standards. One of the conditions used was found to have generated fragments of size 35-47 kb. The DNA from this digestion was ligated with pSuperKos plasmid, a derivative of pSuperCos (Stratagene) digested with AfeI and self-ligated to eliminate the neo marker, pre-linearized with BamHI and XbaI and the ligation mixture was packaged using a Gigapack XIII (Stragene) in vitro packaging Kit and the mixture was subsequently used for infection of Escherichia coli DH5α employing protocols supplied by the manufacturer. Approximately 2000 of E. coli transductants were probed by in-situ colony hybridization with DIG labeled Sb3/7-31 (KS^(q)), Sb1/5-75 (KS3) and and Sb1/5-78 (KS7). Plasmids from 15 colonies, which showed strong hybridization signals were isolated, digested with BamHI and subjected to Southern blotting employing the KS^(q) or KS7 amplimers as probes. Ten plasmids showed strong hybridization with one or both amplimers. The ends of the insert in each of the 10 plasmids were sequenced using convergent primers for each (T7 promoter and T3 promoter). Two cosmids, pKOS146.185.1 and pKOS146.185.10 were found to possess high homology at one end with a segment of the PKS from the tylosin biosynthesis cluster. These two plasmids also each gave rise to DNA fragments of ca. 1 kb and 1.2 kb after BamHI-digestion.

[0097] Identification of chalcomycin biosynthetic gene cluster. Further verification that cosmids pKOS146.185.1 and pKOS146.185.10 contained the chalcomycin biosynthesis cluster was performed by PCR. Specific primer pairs were designed for the chalcomycin KSq (Sb3/7-31 forward 5′-CGTCAGCCTGATCCTCGCCGA-3′[SEQ ID NO:49]; reverse 5′-TCCAGGTGGCCGACGTTC GTC)[SEQ ID NO:50], KS3 (Sb1/5-75 forward 5′-AACGAGATCCCGCCGGG CCTC-3′[SEQ ID NO:51]; reverse 5′-ATCA CGCGTTGCTGGGCGAGG-3′[SEQ ID NO:52]) and KS7 (Sb1/5-78 forward 5′-GGACGTCTGCCGGAGG GTTCC-3′[SEQ ID NO:53]; reverse 5′-GGCCCGTTGGGCACGGACAGA-3′[SEQ ID NO:54]) amplimers and used in PCR reactions with each of the 8 KS amplimers using the following conditions: total reaction volume of 50 μl contained 20-100 ng of plasmid DNA containing an amplimer, 100 pmol of each primer, 0.2 mM dNTP,10% DMSO and 2.5 U Taq DNA polymerase. Cycle steps were as follows: denaturation (94° C.; 40 sec), annealing (55° C. for KSq and KS3 specific primers, 65° C. for KS5 specific primers; 30 sec), extension (72° C.; 60 sec), 25 cycles. Each primer set was found to amplify its cognate amplimer exclusively, with the exception of the primer set for KS7, which was also seen to give a small amount of amplification of non-cognate amplimers. Each primer set was then used for PCR with cosmids pKOS146.185.1, pKOS146.185.10 and pKOS146.185.11 employing the same conditions as described above but using cosmid DNA in place of the plasmid-containing amplimer DNA. pKOS146.185.1 gave correctly sized amplimers with KSq and KS3 primers but not with KS7 specific primers, whereas pKOS 146-185.10 gave a correctly sized amplimer with KS7 but not with KSq and KS3 specific primers, indicating that pKOS146.185.1 contained the 5′ region of the chalcomycin PKS genes.

[0098] The sequence of the insert of pKOS146.185.1 corresponds to bases 1 to 48,595 of SEQ ID No.1 and the sequence of the insert of PKOS146.185.10 corresponds to bases 44,218 to 85,915 of SEQ ID No.1. Table 2 below provides open reading frame (ORF) boundaries corresponding to the nucleotide position in SEQ ID NO:1 (Table 3) of the chalcomycin PKS as well as the nucleotide sequences encoding enzymes involved in precursor synthesis and chalcomycin modification. In addition to the ORFs listed in Table 2, SEQ ID NO:1 includes additional open reading frames of genes encoding proteins or domains thereof that may be useful in the biosynthesis of chalcomycin and/or analogs thereof in certain host cells. The various open reading frames, module-coding sequences, and domain encoding sequences shown in Table 2 and the figures are sometimes referred to as “subsequences.” Those of skill in the art will recognize, upon consideration of the sequence shown in Example 1, that the actual start locations of several of the genes could differ from the start locations shown in the table, for example due to the presence in-frame of codons utilizable by the initiator methionine tRNA in close proximity to the codon indicated as the start codon. The actual start codon can be confirmed by amino acid sequencing of the proteins expressed from the genes. TABLE 2 Chalcomycin PKS and modifying gene cluster ORFs of SEQ ID NO: 1 * “C” encoded by complement of SEQ ID NO: 1 ORF boundaries Name Proposed Function (homology) Strand* No. residues   1-1009 Orf1 Orf1 complement C  343 [SEQ ID NO: 2] integral membrane protein (homolog of S. coelicolor SCF51A.28c)  1121-1963 Orf 2 Orf2 complement C  280 [SEQ ID NO: 3] (homolog of S. coelicolor SCF51A.29c)  3008-3889 Orf3 Orf 3 complement C  293 [SEQ ID NO: 4] Oxidoreductase (homolog of M. tuberculosis MLCL581.18c)  3991-5208 chmCIV 3,4-dehydratase, D-chalcose pathway (EryCIV C  405 [SEQ ID NO: 5] homolog)  5339-6118 chmMIII D-chalcose O-methytransferase (SpnH homolog) C  259 [SEQ ID NO: 6]  6239-7696 chmCV D-chalcose pathway (EryCV homolog) C  485 [SEQ ID NO: 7]  7761-10271 chmR beta-glucosidase, extracellular reactivator of C  836 [SEQ ID NO: 8] chalcomycin (OleR, DesR, EryBI homolog) 10306-11511 chmPII P450 C12, C13-epoxidase (MycG homolog) C  401 [SEQ ID NO: 9] 11549-12772 chmPI P450 C8-hydroxylase (OleP homolog) C  407 [SEQ ID NO: 10] 12762-13610 chmI TEII (homolog of TEII of tylosin cluster [the predicted C  282 [SEQ ID NO: 11] product of ORF5 of GenBank accession # AF145042]) 13631-14602 chmAII TDP-glucose 4,6-dehydratase C  323 [SEQ ID NO: 12] 14648-15562 chmAI TDP-glucose synthase C  305 [SEQ ID NO: 13] 15869-16459 chmJ 3-epimerase; D-allose pathway (TylJ homolog) C  196 [SEQ ID NO: 14] 16523-17290 chmMII D-mycinose 3′ OH-MT (TylF homolog) C  255 [SEQ ID NO: 15] 17551-18810 chmHI P450 C20-hydroxylase (TylHI homolog)  420 [SEQ ID NO: 16] 18831-19052 chmHII Ferredoxin (TylHII homolog)  73 [SEQ ID NO: 17] 18959-20029 chmD D-allose pathway 4-KR (TylD homolog)  326 [SEQ ID NO: 18] 19049-20029 chmD Alternate N-terminus    [SEQ ID NO: 19] 20062-21273 chmMI D-mycinose pathway 2′ OH-MT(TylE homolog)  403 [SEQ ID NO: 20] 21329-22576 chmN D-allose glycosyltransferase (TylN homolog)  418 [SEQ ID NO: 21] 22653-23495 chrB Resistance determinant; 23S-rRNA N1- C  280 [SEQ ID NO: 22] methyltransferase (TlrB homolog) 23622-36947 chmGI PKS, Modules 0-2 4441 [SEQ ID NO: 23] 23823-25046 KSOq PKS Ketosynthase 0q loading domain 25353-26396 AT0 PKS Acyltransferase loading domain 26499-26756 ACP0 PKS Acyl carrier protein loading domain 26808-28079 KS1 PKS Ketosynthase 1 domain 28386-29432 AT1 PKS Acyl transferase 1 domain 30099-30794 KR1 PKS Ketoreductase 1 domain 30966-31220 ACP1 PKS Acyl carrier protein domain 31296-32567 KS2 PKS Ketosynthase 2 domain 32889-33932 AT2 PKS Acyl transferase 2 domain 33975-34574 DH2 PKS Dehydrogenase 2 domain 35472-36257 KR2 PKS Ketoreductase 2 domain 36402-36659 ACP2 PKS Acyl carrier protein 2 domain 37041-42965 chmGII PKS, Module 3 1974 [SEQ ID NO: 24] 37143-38414 KS3 PKS Ketosynthase 3 domain 38724-39869 AT3 PKS Acyl transferase 3 domain 39903-40544 DH3 PKS Dehydrogenase 3 domain 41442-42281 KR3 PKS Ketoreductase 3 domain 42411-42668 ACP3 PKS Acyl carrier protein 3 domain 43022-54388 chmGIII PKS, Modules 4 and 5 3788 [SEQ ID NO: 25] 43139-44422 KS4 PKS Ketosynthase 4 domain 44750-45796 AT4 PKS Acyl transferase 4 domain 46436-47248 KR4 PKS Ketoreductase 4 domain 47318-47575 ACP4 PKS Acyl carrier protein 4 domain 47651-48925 KS5 PKS Ketosynthase 5 domain 49226-50272 AT5 PKS Acyl transferase 5 domain 50309-51001 DH5 PKS Dehydrogenase 5 domain 52085-52957 ER5 PKS Enoylreductase 5 domain 52925-53728 KR5 PKS Ketoreductase 5 domain 54439-59277 chmGIV PKS, Module 6 1612 [SEQ ID NO: 26] 54544-55818 KS6 PKS Ketosynthase 6 domain 56122-57168 AT6 PKS Acyl transferase 6 domain 57844-58707 KR6 PKS Ketoreductase 6 domain 58753-59019 ACP6 PKS Acyl carrier protein 6 domain 59387-63439 chmGV PKS, Module 7 and TE 1350 [SEQ ID NO: 27] 59489-60778 KS7 PKS Ketosynthase 7 domain 61112-62209 AT7 PKS Acyl transferase 7 domain 62276-62533 ACP7 PKS Acyl carrier protein 7 domain 62549-63436 TE Thioesterase 63522-64760 ChmCII NDP - hexose 3,4-isomerase; D-chalcose pathway  412 [SEQ ID NO: 28] component (EryCII homolog) 64804-66081 ChmCIII Chalcose glycosyltransferase (EryCIII homolog)  425 [SEQ ID NO: 29] 66194-66940 ChmU Post PKS Ketoreductase (SimJ2, NovJ homolog)  248 [SEQ ID NO: 30] 67323-68471 Orf4 Permease homolog (SCF6.09 homolog) C  382 [SEQ ID NO: 31] 68733-70196 Orf5 Membrane protein homolog (SC66T3.03 homolog) C  487 [SEQ ID NO: 32] 70193-70888 Orf6 D-alanyl-D-alanine carboxypeptidase homolog C  231 [SEQ ID NO: 33] (SCD6.17c homolog) 71382-72542 Orf7 Sensory histidine kinase homolog (SCE94.10 C  386 [SEQ ID NO: 34] homolog) 72638-73324 Orf8 Two-component syst. response regulator homolog C  228 [SEQ ID NO: 35] (SCE94.09 homolog) 73651-75081 Orf9 permease (xanthine/uracil permease type) (SC9G1.02, C  476 [SEQ ID NO: 36] SC9G1.04 homolog) 75401-76117 Orf10 SC6A11.03c Homolog C    [SEQ ID NO: 37] 76537-78375 Orf11 Permease homolog (SC9G1.02, SC9G1.04 homolog)  612 [SEQ ID NO: 38] 78521-79192 Orf12 MerR-family transcriptional regulator (SC1A4.06c  223 [SEQ ID NO: 39] homolog) 79228-79983 Orf13 Type-II thioesterase (SanP homolog) C  251 [SEQ ID NO: 40] 80489-81439 Orf14 Open reading frame C    [SEQ ID NO: 41] 81806-82528 Orf15 Response regulator homolog (SCD49.02c homolog)  240 [SEQ ID NO: 42] 82712-85912 Orf16 Open reading frame    [SEQ ID NO: 43]

[0099] Genes listed in Table 2 that encode proteins with post-PKS polyketide-modifying activities include: chmPI, chmPII, chmHI (P450 homologs), chmN, chnCIII (glycosyltransferases) and chmU (polyketide ketoreductase).

[0100] Genes listed in Table 2 that encode proteins predicted to participate in the biosynthesis of sugar residue subunits of chalcomycin or modification of sugar residues after their addition to the polyketide include: chmCIV, chmMIII, chmCV, chmAII, chmAI, chmJ, chmMII, chmD, chmMI, and chmCII. Of these, three are predicted to participate in D-chalcose residue biosynthesis (ChmCII, ChmCIV and ChmCV), two are predicted to participate in D-biosynthesis allose residue biosynthesis (ChmD and ChmJ) two are predicted to participate in conversion of the D-allose residue to D-mycinose residue after covalent linkage of the D-allose to the polyketide (ChmMI and ChmMII), two are predicted to provide precursors for both the allose and chalcose pathways (ChmAI and ChmAII), and one is predicted to O-methylate the chalcose residue (ChmMIII).

[0101] As noted above, the invention also provides inter-polypeptide linker sequences, which can be identified by the skilled reader (e.g., comprinsing the sequences between the N-terminus of the polyptide and the beginning of the first KS domain; or between the C-terminue of the polypeptide and the beginning of the last ACP domain) and polynucleotides encoding such linkers. TABLE 3 Chalcomyin PKS cluster from Streptomyces bikiniensis NRRL 2737 (SEQ ID NO:1) 1 GGGGCCCGCC GGACGGGGCT GCCCGGCTCT CGGCGGTGCC CGGTGGGCCG GGTGCGGGCT 61 CGCCCGCGGC GAGATGCTCC AGGACCTCCG CCAGTTCCCG GCAGGCGCGG CGTACCGAGC 121 GGCGGGTCGC ACGCTGCTCC GTGATGACGG AGGCGAGAAG CAGGGCGGTC AGTGCGGCGG 181 AACCGTTGAA CGCCTGGAGC TTGGCCATGA TCTCGACGTC CGAGAGGTGG AGGAACCCTC 241 CCCGTCCGGC GTTCGCCTCG AAGGTGGCGA GCACGGAGGC GAAGAGCGCG CAGAGCATGC 301 TTCCGGTGAG CTGGAAGCGG AGCGCCGCCC AGATCAGCAG GGGGAAGACG AGGAAGAGCA 361 TGCCCACCGG GCTGAGCACG GCCATGGGCA TGAGGATCAG GGTCGCGAGA CCCAGCAGGG 421 CCGCCTCCTT CCAGCGCCGT ACGCGGAACC GTCCGGCCGG CCCCGCGAGG ACGAGGAGGA 481 GCGGGGCGAC GAGCAGCACC CCCATCGTGT CGCCCACCCA CCAGGCCAGC CAGACGGGCC 541 AGAACTCGGT CGTGTCCAGG GAGCTCTTCG CCACCTGCAG TCCGACCCCG GCGGTCGCGC 601 TGATCAGCAT GGCGCCGAAC CCGCCGAGGA AGACCAGGGA GAGTCCGTCC CGCAGCCGTG 661 CCATGTCGAG CCGGAAGCCG GCCCGTGTCA GCAGCAGGAA GGCGCAGAGC GGCGCGACGG 721 TGTTGCTGAC CACGGTGACC ACGGTGGTGG GCCCCGGCGT GGTGAGGGAG GCGATGACGA 781 GGAAGGAGCC GAGGGCGATC CCGGGCCAGA CGCGCGCGCC GAGCAGCAGC AGGGCGGCGA 841 CGGCGACGCC GGTGGGAGGC CAGATGGGGG TGACCACCAC GCCTTCGACG ACGAGGCGGC 901 CCATCAGGCC GAGTCGTCCG GCCGCGTAGT AGAGCACCGC CACGGCCAGC GACATCAGCG 961 CCGTCGCCGC GGGGGACCGG TACTGCCGAA TATCCAACAC GTCTGCCATC AGACACCGAC 1021 CGGGTTGCCG CGCCCCTGCA TGGCCGCCTG CGTGTCGGGG ACACGCCGCC CGGCCCGGAC 1081 CGGGCCGCGG GGAGGACCGG CCCGAGGCGG GTCCCCTCGC TCACTCCCCG GTCGCCGGCC 1141 GGGGCGGACC GCCGTCGTGG CCGACGACGA GGACGGCCGC GTCGTCCTCG TGCCCCACCG 1201 TGGCCGCCAG TCGCATGACG GCGGTGGCGA GCGCGTCGAC GTCCAGCCCG GCGACGGCCG 1261 TGATCCCGGC GAGTCTCGTC ACCCGGTCGA GACCCTCGTC GATGTGGAGC GAGGGCCCCT 1321 CCACGACCCC GTCGGTCAGG AGGACGAAGA CGCCGTCGGC GGTGAGCCGG TGGCGCGTGG 1381 CCGGGTAGTC GGCGCCGCGC AGCACGCCGA GAGGAGGCCC GCCCTCGCTG TCCTCGATGC 1441 CGGAGCGGCC GTCGGCGGTG GCCCAGATGT GGGGGATGTG GCCGGCCCGG GCGCATTCCA 1501 GGGTGCCGGC GGCGGGGTCG AGCCGCAGGA AGGTGCAGGT GGCGAAGAGG TCGGCGCCGA 1561 GGGAGACGAG CAGGTCGTTG GTGCGGCCGA GCAGCTCTCC CGGGTCCGCG GTGACGGAGG 1621 CCAGCGCGCG CAGTGCCACG CGGACCTGTC CCATGAAGGC GGCGGCCTCG ATGTTGTGTC 1681 CCTGGACGTC GCCGATGGAC ATGCCGATCC GCCCGCCAGG CAGGGGGAAG GCGTCGTACC 1741 AGTCGCCGCC GACGTTGAGC CCGTGGTTGG CGGGCTCGTA CCGGACGGCC AGCCGGGCAC 1801 CCGGAAGACT GGGCAGGTCC GAGGGCAGCA TGCCGCGCTG CAGGGCCACG GCGAGCTCGA 1861 CACGGGACCG CTGCGTCTCG GCCAGCTCCC GCGCCCTGGC GGTCAGCGAC CCGAGCCGGA 1921 CCAGAAGGTC CTCGCTGCTG TCGGCCGGGC GTCTGCGGAA CATCGATCAC TCCGACGTCA 1981 CGACAATCCT CGCATCACTC CGTCCCGTCT CCAGCACGCG GGACCACAGG GGACCACCCC 2041 GGTACGAACA GGTCCTTCCC ACTGTGCCCG GAGGGGGCGG GGTCCGCATC TCATCGGCGG 2101 GAGAGCGCGG TGGATCCCAG GGGGCCCGCT CAGGTCACCG AAAACGAGCA AACGTTCGAT 2161 AATGTGGTCG CGCCGGTCTG TGCGGCCGTT CAGCGTTCGA CGGTCACTGC GGCGGCCGCG 2221 ATGCCGTCGC GCACCAGCCA CCGGCCGGTG AACCCGCCCA GCTGCCGTCC GTCGACCGTC 2281 GGCCCGGGCA CGAGCAGCCG GGCCCTGAAA CGGCCGCCCG GCTGGAAGTC GACGGCCGCC 2341 TCCCCGAAGT CGAGCCGGCT CCGGGTGAGC GGGAACCACG CCTTGTAGAC GGCCTCCTTG 2401 GCGCAGAACA GCAGCCTGTC CCACGGGATG CCGGGCCGGG CCAGTGCCAG AGCGGCCAGC 2461 GGCCCGCGCT CATCCGCGGT CGTCACCGCC TCGAAGACGC CGTGCGGCAG CGGAAGGGCG 2521 GGCTCGGCGT CGATGCCCAG AGACGCCACG TCCGCCTCGG ACGCCACCGT CGCGGCGCGG 2581 TAGCCGGCGC AGTGGGTCAT GCTGCCGACG ACACCGGGCG GCCATCCCGG CGCACCCCGC 2641 TCACCGGGCA CGAGGGCCAC CGGCCCCCAC CCCAGACCGG CCAGCGCGCG TCGCGCGCAG 2701 AAGCGCACGG AGGTGAACTC CCTGCGTCGC TTGTCGACCG CGCGCCCGAT CGCCTTCTCC 2761 TCGTCGGCGA ACAGCCGCGC CTCGGGGTAC CGGTCGGCAT CCAGGACGTC GCCGAAGACG 2821 TCCACCGACA CCGCGGCGGG CGGCAGCAGT GCGCAGATCA GCCCGGCCCA CCGCGGCACC 2881 GACACGGCGG CGTCGGCCTC GGCACGGTCG TGCACGCACG CCGACGCCGC GGCGTCGGCG 2941 AGGGGGCCCG TGCGGCTGCC GTCCCCGGAC CGCCGCGCCG AGGACGCCGC CGGCGGGAAG 3001 CCGTCCCTCA CACGGGCACC GTGGCGTCGT CGTGCGTGCG TCCGAGCGCG TTCAGCCGGG 3061 CCAGCTGGCC ATCGGAGAGA GCGATGCCCG ACGCCGCGAC GTTCTCCCTC AGATGCGCGG 3121 GCGAGCTGGT GCCGGGGATG GGAATGACCG CCGGCGAGCG GTGCAGCAGC CACGCGAGCG 3181 CCACCTGACC GGCCGACACC TCCAGCTCGG TGGCGATGTC GGCCACCGGG CTCCCCCCGG 3241 CGGCGAGCGC ACCGCGGGCG ATCGGCAGCC AGGCGATGAA CGCGATCTCG TGCTTCTCGC 3301 AGTACTCGAC CACCTCGTCG TTGCGCCGGT CGGTCAGGTT GTACACGTTC TGCACGCTGG 3361 CCACGGTGAT GTGCTCACGG GCGGCCTCCA CTTCCCGGAC GGTGACCTTG GACAGCCCGA 3421 TGTGCCGGAT CTTCCCTTCG TCCTGCAGTT CCCCGAGCGC ACCGAACTGC TCGGCCGCCG 3481 GCACCTTCGG ATCGATCCGG TGCAGCTGGA AGAGGTCGAT GCGGTCGAGT CGCAGCCTGC 3541 GCAGGCTCAG CTCGGCCTGC TGGCGGAGGT ACTCCGGTCG GCCGCACGGC ACCCACTGGT 3601 CGGGACGGGG CCGGCACTGT CCGGCCTTCG TCGCGATCAC GAGGCCGTCG GGGTACGGGC 3661 GCAGTGCTTC GGCCAGCAGC TCCTCGTTGC TTCCCAGCCC GTAGGAATCG GCCGTGTCGA 3721 TGAAGGACAC ACCGAGGTCC ACGGCCAGCC GGGCCGTGCT GATCGCAGCC TCCCGGTCCT 3781 CCGGCGGGCC CCAGTACCCC GGACCGGTCA GCCGGAGGGC GCCGAAACCC AACCGGTGTA 3841 CCGAGAGGTC GCCTCCCAGA GGGAAGGTGG TCCTGCCGGG CTGTGCCATG CGTTCCTCCT 3901 GGACGACGTC CGTGCACTCG GGTGGGGCGC GTGGTGACCT CGGTGGGGGC GGGCCGATGC 3961 CGACCGTCCG AACACGGTGG ATCCCCCGGT TCAGGGAGCC GTCGTGGAGG GCACCCGCTC 4021 GTCGGCCCGT CGGGTCACCT CGTGTCCCCG CTCCAGAGTG AGCCGCACGA TGTCGCAGAC 4081 CCGACGGATG TCCTCGCGAG AGACGGTGGG GCCGGTGGGC AGGGCGAGGA CCTTCCGCGC 4141 GAGCCGTTCG GTGTGGGGCA GGGAGACCGG CCGCTCCGAG CGGTAGGGCT CCATCTCGTG 4201 GCATCCGGGG GAGAAGTACC GCTGGCACAT GATGTTCTCC GCCCTCAGCA CCTCGTCCAG 4261 CAGGTCCCGG TGGACCCCGG TCACCGCGGC GTCGACCTCC ACGACCAGAT AGTGGTAGTT 4321 GTTGCGCTCG GCACGGTCGA ACTCCATGAC CTTCAGCCCG GCGAGCCCGG CGAGTTCCGA 4381 CCGGTAGTCG TCGTGGTTGG CCTCGTTCCG GCGAACCGTC TCCTCGAAGG CGTCGAGCGA 4441 GGTGAGTCCC ATCGCGGCGG CGGCTTCGGT CATCTTCCCG TTGGTGCCGG TCTCCGTGGA 4501 CACCCGCCCC TGGGTGAATC CGAAGTTGTG CATCGCGCGG ACCCGCTGGG CCAGCCTCTC 4561 GTCATCGGTC ACCACCGCGC CGCCCTCGAA GGCGTTGACC ACCTTGGTGG CGTGGAAGCT 4621 GAACACCTCG GCTTGTCCGA AGCCGCCGAT CGGCTGCCCT TCCGACGTGC AGCCGAGTCC 4681 GTGCGCGGCA TCGTAGAAGA GCCTGAGACC GTGATCGGCC GCGACCTTCG CCAGCCGGTC 4741 GACCGCGCAG GGCCGACCCC ACAGATGGAC CGGCACGACC GCACTCGTAC GGGGGGTGAT 4801 CGCCGCCTCG ATCAGATCCG GGTCCAGGCA GTTGGTGGCC GGGTCGATGT CCACGAAGAC 4861 CGGGGTCAGA CCCAGCCAGC GGAACGCCTG GGCGGTCGCC GGGAAGGTCA GCGACGGCAT 4921 GATGACCTCG CCCGACAGAT CGGCGGCGCG GGCCAGCAAC TGGAGGGCGA CGGTCGCGTT 4981 GCAGGTCGAC ACGCAGTAGC GCACGCCGGC GAGTTCCGCC ACGCGCTGCT CGAACTCCCG 5041 GGCCAGCGGC CCGCCGTTGG TCAGCCACTG GTGGTCCAGC GCCCAGTTCA CACGGTCCAG 5101 GAACCGCGCT CGGTCGCCCA CGTTGGGCCG CCCCACGTGA AGTGGTTGCA GGAACGCCGA 5161 CGGGCCGCCG AACACGGCGA GATCACCGAG ATTGCGTTTC ATGGTCATAC CTCCCCGGTG 5221 CACGGGACGG TGCACCCGGC AGCAGCCGGC ACAGGACGTG GACGTACCGG AGGGACAGGG 5281 GCCGCAGCGC ACGACGGCGT CTCCGTCGTG CGTACGCGAA AGGGGCGCAC GGAACGGATC 5341 AGTGCTCGCG GCGCCAGTAG ACGCCCGTCA CGTCCACCGT CTCGATCGGC TCGTCGATGC 5401 CGTGTTCGCT CCGGTAGTCG TGGACGGCCT GCTTGCACGC CGGGATCAGG TAGTCGTCCA 5461 CGATCACGAA CCCGCCCACG GACAGCTTGG GGTAGAGGTT GACCAGCGCG TCCCTCGTCG 5521 ACTCGTACAG GTCGCCGTCC ACCCGCAGCA CCGCGAGCCG GTCGATCGGC GCGGTCGGCA 5581 GCGTGTCGGC GAACATGCCG GGCAGGAACC TGACCTGCTC GTCCAGCAGG CCGTAGCGGG 5641 CGAAGTTCTC CCTCACCTGC TCCTCGGAAC AGCTCAGTAC CCAGTTCAGG TGGTGGAACT 5701 CCATCGCCCG GTCGAGCGGG TGGCTGTCCT CGGACGTCAC CGGGACACCG GCGAACGAGT 5761 CGGCGAGCCA CACGGTGCGG TCCTCCACAC CGTGCGCCTT GAGGAGCGCG CGCATCAGGA 5821 TGCAGGCGCC GCCGCGCCAC ACGCCGGTCT CGATGAGATC ACCGGGAACA TCGTCCTGGA 5881 GGACCCTCTC CACGCACCTC TGGATGTTGT CCAGGCGTTG CAGGCCGATC ATGGTGTGCG 5941 CGACCGTCGG CACGTCCAGT CCTTCGGCCC GGTGGTCGGC GTCGAAGGTC CCGCGCTCGA 6001 CGTCCGGGCC CTCCGCCCCC GGACGCATGC GGTCCGCCAG TTCCTTGTCC AGGACGTTCA 6061 TCCCGACCGG GAAGGTCGGG TGATCCCCGT AGATGGTGTT CGACACGACG TTCTTCATGA 6121 GGTCCACGTA GAGCTCGCGG GTCTGCACGG TCGACTTACC TCCGGCTAGA TATCGAACAG 6181 AGAGAGAATG TGCGGGGCGA CGGCGTCCGC GGACGCGGTG GGAGCCGTCG CGGTCGGGTC 6241 ACCTCAGGAA GCCGCGCGCG TCCTCCCAGC CGGCCACGAC ATCGGCCTCC AGCTGGTTGA 6301 GCCGCGCCGC CACCACCTGG TCGAACCCGT CCATGAAGTA CTCGTCACCG GCGTGCGGCG 6361 CTATCAGACG GCCGTCGTCC ACGAACCGCT CGACGACCTC CGTCAGGGAG GTGCCCGGCC 6421 CCACCCGGCC CGCGACGTAC CGGTCCGCTC CGGTGAGATC CGGGAACCCC GCCTCCCGGT 6481 ACAGGTACAC GTCACCCAGC AGGTCCACCT GTACGGACAC CTGGGGATGC GCGGACCGGC 6541 GCATGGTTCC GGGCCTGATC CTGAGCAGCT CGGCGTCCGC GCCGGTCTTC AGGCTGTGCA 6601 ACGCGTAGCC GTAGTCGATG TTCAGCGTGG GGGTCCGCCG GCTCACCGCC TCCTCGAACG 6661 CGAGCAGCCC CTCCTGGAGT TCGGCGCGTT CGGCCTCGAA CAGCCTGCCG TCCTCCCGGC 6721 CGCTGTAGTC CTCGCGCACG TTCAGGAAGT CCACCGGCCG GTCCGGCGCG GCCTCGTTCA 6781 GGTCGGCGAT GAAGTCGACG AGGTCGAGCA GCCGGTGGAC GCGCCCGGGC AGCACGATGT 6841 AGCTGAGCCC GAGCCGGATC GGGCTCTCCC GCTCGGACCG CAGCTGCTGG AAGCGCCGCA 6901 GGTTGGCGCG GACCCTTCCG AAGGCGGCGC GCTTGCCCGT GGTCTCCTCG TACTCCTCGT 6961 CGTTCAAGCC GTACAGCGAG GTGCGCACCG CGTGCAGGTC CCACACCCCG GGCTGCCTGT 7021 CCAGCGTCCG CTCGGTGAGC GCGAACGAGT TCGTGTACAC GGTCGGCCGC AGCCCGCGAG 7081 CCGCCGCACG GCTGCTGAGC GCGCCCAGGC CCGGGTTGGT GAGGGGCTCC AGACCGCCCG 7141 AGAAGTACAT GGCGTACGGG TTGCCGGCCG GGATCTCGTC GATGACGGAC GCGAACATCG 7201 CGTTGCCGGA CTCCAGCGCC GACGGGTCGT ACCGCGCACC GGTCACCCGG ACGCAGAAGT 7261 GGCAGCGGAA CATGCAGCTC GGCCCCGGGT ACAGGCCCAC GACATAGGGG AAGGCCGGCT 7321 TGTGCGCGAG CGCCGCGTCG AAGACCCCCC GTCGCTCCAG CGGCAGCAGG GTGTTCTGCC 7381 AGTACTTGCC CGCCGGCCCG TTCTCCACGG CGTGGCGCAG CTCCGGGACA CGGCCGAAGA 7441 GGCCGAGGAG CCGGCCGAAG GAGGCCCGGT CCACGTCCAG CATCCGGCGT GCCTCCTCCA 7501 GGGGCGTGAA GGGGTGGTTC CCGTAGCGCT CGGCCAGCCG CACGAGCCGG CGCGCGACCG 7561 TCGGGCCCTC GTCGACACCG ACGCGGCCGT CGGAGACCAG GGCGCGGTGC ACCGTGTGGA 7621 CCGCTGCCGG CAGGTCGGCG CCGGGGCGGG CGCACAGGGC GACCGGATCG GCCGCGGTGG 7681 AGGCGTGCGA GGTCATCCTT CGTGTCCAAT CGTCTGCGTC CGGAGGGTCG GTCCGTTCCC 7741 CGGGAAACGC GGCGGGGCGG TCACCGGGAC GGCACCGTGA CGGATGTGGT CAGGGACGTC 7801 TCGGCCGCGG ACGGGCCCAC GTGTACGGCC CTCCTGCCGG TGCCCGGCTT CCACGTGCCG 7861 GCGGCGGTGT CCCAGTAGCG CAGTTGCTGC TCGTCGACGG GGACGGTGAC CCGCCGCTGT 7921 TCTCCCGGCC GGAGGGTGAC CTTGGTGAAT CCGGCGAGTT TGCGCAGCGC CTGGGGGGCC 7981 TGGGTGTCCG GACTTGCCCC GAGGTAGACC TGGACGGTCT CCCTGCCCGC CCGGTCACCG 8041 GTGTTGCGGA CGGTGACCGT GGCCTCCAGC CCCCGGGCGG TGCGCGCCAC GGACAGGTCG 8101 CTGTAGGCGA AGGTGGTGTA CGACAGGCCG TACCCGAACG GGAAGAGCGG GGCCACGCCG 8161 GTCCGGTCGT ACCACCGGTA GCCGACATCC AGTCCCTCGG AATAGGTCTC CTTGCCGTCG 8221 ACACCCGGGT AGCGGTGCGG GTCACCGGCC ATGGGATGGC CGGTCTCGGT CCCCGGGAAG 8281 GTCTGGGTCA GCCGGCCGCT GGGATTCGCG TCGCCGAACA GCAGGGCAGC GGTGGCCTCC 8341 GCGCCCTCCT GCCCCGGGTA CCACATCTCC AGTACGGCGG CCGTCTCACG CAGCCAGGGC 8401 ATGAGCACCG AGGAACCGGT GTTGAGGACG ACGATCGTGC GGGGGTTGAC CTTGGTGATC 8461 GCCGCGATCA GCTCGTCCTG TCGGCCGGGC AGGGACAGCG AGGACCGGTC CACGCCCTCG 8521 GCACTGTCGT CGTGGGCGAA GACGACGGCG GTGCGGGCCT CGGCCGCCGC CGCGACGGCG 8581 CGGTCGAAGT CGTCCCGGGC AGCCTCGGGA GTGACCCAGC TCAGCTCCAC CGACAGCGGG 8641 GTCTGTTCGA AGGCCCAGCC GTTCATGGTC ACCGCGTGGG TGCCGCGGGT CAGCCGCATC 8701 GTGGTGGTGA CGGTGCCGAA CGCCTCGGTG CCGAGGACAG CGGACTGCCC CGCGATCTGC 8761 AGGTTGGCGA CCCCGCCGAC GGCGGTGAAG GCGATCTTGT AGTCGCCGTC GGCGGGGACG 8821 GTGAGCCGAC CCTCGTAGAA GACGCCCTGG CCGCTGGGAT CCAGTTGCTT CCCGCTCGTG 8881 AAGGCGGGGG TGAGCGAGCT TTCGGGCACG GGCACGCCGA CCAGGTCCTC ACCGGGCTCG 8941 TGGACGACCC GGGCCTTCTC GCCGGCGCGC CGTGCGAGGG CGTCGACGGG TGCGGTCGCC 9001 CGGTCGGGTA TGACGTGCGC GCTGCCGTTG CCGGTGACCT TGGGGTGCTT GGCGCTGTTG 9061 CCGATGACGG CGATGTCCGT GGCGTCCTCA CCGGTCAGGG GCAGCGTCCG GCGCTCGTTG 9121 CGCAGCAGCA CCCCGCCGTT CTCGGCGATG GTGCGGGCCG CCGCGCGGCC GGCCTCGGGA 9181 TCACGCTGCG GGCGCTCGGT CGCCTTGCCG TCGAGCAGGC CGAAGCGCTC CATCTGGCCG 9241 AGGATGCGGA CGACGGACCG ATCGAGCGTC GCCTCGGGGA CGCTGCCGTC CCGCACGGCG 9301 GCCCTGAGCG CGGAGGAGAA GTACTTCGAT TCCGGCACCG GCTGCCCCAG GGTCAGCTCG 9361 ACGCCCAGTT CCTGGTCGAG GCCCCTGGTG ATGTCGCCGG TGGCGTGGGT CGCCAGCCAG 9421 TCGGACACCA CCCAGCCGCG GAAGTCCCAC TGTTCGCGCA GCACCTCCTG CAACAGGTGC 9481 TCGTTCCCGC ATGCGTGCGC GCCGTTGACC TTGTTGTACG AGCACATCAC CGAGGCGGCG 9541 CCCGCCCGCA CGGCGCTGCG GAAGGCCGGC AGCTCCACCT CCTGGAGCGT CTGCTCGTCG 9601 ACCACGGCGT CGATGGTCTC CCGCTGGTAC TCCTGGTTGT TCGCGGCGAA GTGCTTGACC 9661 GTGGCCATCA GGCCCTGGTT CTGGATGCCG CGGACCTCGT GGGCGGCCAT CCGGGACGAC 9721 AGCAGAGGAT CCTCGCTGTA GGTCTCGAAG TTCCGCCCCG CGTGCGGCAC CCGGATGACG 9781 TTGGTCATGG GACCGAGGAC GATGTCCTGT CCGAGGGCCC GTCCCTCCCG GCCCAGGACG 9841 GTGCCGTACT CCTCGGCGAG GCGTTCGTCG AAGGTGGCGG CGAGCGCCAC GGGGGTGGGC 9901 ATGGCGGTGG CGGTACCGCC GAGCAGACGG ATGCCGACCG GGCCGTCGGC GGTGCGCAGC 9961 TCGGGGATGC CGAGCCGGGG CACGCCCGGC AGATAGCCGA TGCCGGTCAT GGTCGGCCCG 10021 CCCACGGGCC CGGTGGTCCA GTGGACGAAC GAGATCTTCT CGTCGAGGGT CATCTTCGCC 10081 ACCAGCCCGC GCACCCGCGC CGTCCCGGGC TCGGCGGCCG GAGCACCGGC GGCGGAGGGG 10141 GCGGTGAGCA GACCGCCGAC GCACAGGGCC GCGAGCGCGG ATCCGACGGT GCGCCGGATG 10201 CGGCGACCCG TCCTCGTCGT GCCGAACAGC ATGCTGACGG ACGTCCTTTC TGCCGAGGTT 10261 GCCGTCCTCA TCGGGGCGGG AACGTTTCTG TCCGTGCCGC CATGATCACC AGCCCACGAG 10321 CATCGTGCGC GGGCCCCGCA CCACCATCTC CGTCTTCCAC TCGACGGGCT GGGCGAGGTG 10381 CAGCCCGGGG AGTTCGTCGA GCAGGGTCCG CAGCGCCTCC TGGAGCTCCA GCCGCGCGAG 10441 GGACGCGCCG AGGCAGTGAT GCGGACCGTG TCCGTACCCC AGGTGCCGGC CGGCGTCGTC 10501 GCGGGTGATG TCGAGCACGC CGGGCGAGCG GAAGCGCAGG GCGTCCCGGT TGGCGGCGTT 10561 CATCTGGACC AGCACCGGAT CCCCCGCCCG CACCAGCGTC CCGCCCACCT CGACGTCCTC 10621 GGTGGCGTAG CGCGGGAATC CCGCCTGGCT GCCGAGCGGA ACGAACCGCG TCAGCTCTTC 10681 CACCGCGTTG TCCAGCAGGT CAGGACGGTC CCGGAGGAGG GCCAGCTGGT CCGGCTGTTC 10741 GAGCAGGACC AGGACGAAGT TGCTGATCTG GCTGGCCGTG GTCTCGTGCC CGGCGAACAG 10801 GAGGAAGACG ATCAGGTCGA CCAACTCCTC CTGCGACAGC CGGCCCTGGG CGTCACGGGC 10861 CTCGACGAGC GCCGAGACGA GATCGTCTCG CGGCGCGGCG CGGCGGGCCG TGATCAGGTC 10921 CGCCAGATAG CCGGTCAGCT CGCCGGCCAG CCGCACATGG TCCTCGGCGG TGAGCGAGCT 10981 GGTGGACATC GCTATCTCGC ACCAGCCGCG GAACAGGTCA CGGTCCTCCT CGGGCACGCC 11041 CAGCAGGCCG CAGATGACCG CCACGGGAAG GGGGACGGCG TAGTGGTCCA CGAGGTCGAC 11101 GGGCGATCCG AGCGCCGTCA TGTCCCGGAG CAGCGACGCC GTCATCCTTC GGACGTGCGG 11161 CCGCATGGCC TCCACGCGGC GCGGGGTGAA CGCCTTGGTG ACCAGCCCGC GCAGCCTGGT 11221 GTGGTCCGGC GCGTCCATGC CGATGATGCC GTTGGGCGTC CGCAGCTCCC GCATGCGCGG 11281 CGCGTCGTTC TCCGCCTCCG CGGCGTGGCT GAACCGCCGG TCGCCGAGGA CGAAACGCGC 11341 GTCGTCGTAA CGGGAGACGA GCCAGCCCGG CTCCCCGTAC GGCATGTGGA CCCAGAGGAG 11401 TCCTTCGCTC TTCCGCGCCT GCTCGTACGC CTCGTCCAGG TCCAGTCCCT CCGGGCGGCC 11461 GAAGGGATAG GAGACGGGTG CGGTCTTCGT GCTGGTCAAG GGGAGCCCCA TATCGCGTCG 11521 TTCGGGTGCT TAATCGTCGT GGGCCGGATC ATGCGGCCGA GCCGCCCCAG GTGACGGGGA 11581 CCGCCTCGGG GGTGCGCAGG AGGGAGCCGG CCCGCCAGCG AAGCTCACTC GCGGGGACGG 11641 ACAGCCGGAG CTCCGGCAGG CGCTCGACCA GGGTGCTCAG CACGACCTGC AGTTCGAGCG 11701 GGGCCAGGGG GGCGCCCATG CAGTAGTGGG CGCCGTGACC GAAGCCGAGG TGCGGGTTCT 11761 GGGCACGGGC CAGGTCGAGG GAGGCGGCAC CGGGAAACGC CGTGTCGTCG AGGTTCGCGG 11821 ACGCGATCGA GGTGATGACC GCCTCGCCCG CGCGGATGAG CGTGCCGCCG ATCTCGACGT 11881 CCTCCAAGGC GATGCGGGCG AACCCGTCCA GGGTGCTCAG CGGGGTGAAG CGCAGCAGCT 11941 CCTCGACGGC GGAGGGAACC AGGTCAGGTT CGGTCACCAG GCGCTCGTAG AGGCGGCGGT 12001 CGTCGAGCAG GAGGAGGACG AAATTGCCGA TCTGGGTGGC GGTCGTCTCG TATCCGCTGA 12061 TCAGCAGGCC GGAGCCCATC ATGAGGAGCT CGGCCTCGGA GAGCCGGTCG CCTTCGTCAC 12121 GGGCCTGGAC CATGGTGCTG AGGAAGTCGT CGGTGGGCCG GGCGCGGCGA TCGGCCACGA 12181 GGTCGGCCAT GTAGGCGGAG AAGTCCTCGG TCGCCCGCTG CACTTCGGCG GGCCCCAGGG 12241 AGGAGGACAC CAGCGCCTCG GAGAAGTCCC GGAAGAGGTG GCGGTCGTCG TAGGAGACGC 12301 CCAGCAGTCC GCAGATCACG GAGATCGACA CGGGCAGCGC CAGGTCTTCC ATGACCTCGC 12361 CGGACGGCTC GTCGCGCGCG ACCATGCCGT CGAGCAGTTC ATCGGTGAAC CGTGAGACCC 12421 GCGGGCGCAG TTCCTCCACC CGGCGGGCGG TGAACGCCTT CCCGGCGAGC CGCCGGAGCC 12481 TGGTGTGTCC GGGCGGGTCC ATGGAGATGA GACCGCCGGC GGGCAGCGGG TACTCGGTGG 12541 GCCGGGGCAC GTCACGTCCG GCCCCGGCCT CCATGCTGAA CCGCGGGTCT CCCAGGACCG 12601 CCCTCACGTC GGCGTGTCGG GTCAGCAGCC AGGCCTCACC GCCGTACGGC ATGCGGATCC 12661 GGGACACGGG CTCGTGCTCC CGCAGACGGC TGTAGAGCGG ATCCAGCGCG ATGCCCTCGG 12721 GCGGGGAGAA GGGGTACGGG CGAGTCCGGT GGACCGGACA GCTAGACGTC ATGGACACTC 12781 TCTCGGTCGT ACGGGGCGGC GGCAGAGCTC GAAGGGTGCG GGCGGCCGAC GGCGAGCCCG 12841 GTCGCCGTCC GGATCGTCCG GCACACCGCT TCGGCCTGCT CGGTGAGGTA GAAGTGGCCT 12901 CCGGGGAAGG AACGGAACGC CGTCTCCCCG GTGGTCAGCC CGTGCCAGGC CAGGGCTCCG 12961 TCGGTGGGGA CGTGCGGATC CGCGCTTCCC GTCAGCACGG TGATCGGGCA GGCGAGCGGA 13021 GCTCCCGGAC GCCACGTGTA GGTGGCGGCG GCCCGGTAGT CGTTGCGGAT CGCCGGCAGG 13081 GCCATCCGCA GGACCTCCTC GTCGGCCAGC ACCCGGGGGT CGGTGCCTTG CAGTTCGGCC 13141 AGCTTGGCGA CCAGCCGGTC GTCGCTCAGC AGGTGCGCGG TGGTCCGGTG GGCGACGGTC 13201 GGGGCGACGC GGCCGGAGAC GAACAGATGC GCCAGCCTGC TCTCCGGCGC CTGTTCCGCG 13261 AGCCGGCGGG CGGTCTCGAA GGCCACCAGC GACCCCAGGC TGTGACCGAA GAGCGCCACC 13321 GGCCGGTCCA GCCAGGGGCC GAGCGCTCCG GCGACGTGCG TCACCAGAGC GTCGACGGAG 13381 TCCACGAACG GCTCCAGCCG CCGGTCCTGC CGCCCGGGAT ACTGGACGGC GAGCACCTCG 13441 ACCCGGTCCG GCAGCAGACA GGTGAAGGGG AGGAAGGCGC TGGCGCTGCC GCCGGCGTGC 13501 GGAAGGCACA CGAGCCGGAG CGCGGGGTCG GCGACGGGCC GGTAGCGGCG CAGCCAGAGG 13561 TCGCCGGCGT TGGTGGAGCC GGGCGCCGTC GTGGCGGGCC CCTCGTTCAT GCGTGATCCG 13621 CTTCCGGACG TCACGGTGTC AGCGCCTTCC ACCACGTGCC GTTGTCCCGG TACCAGTCGA 13681 CGGTCTCCGC GAGCCCGCGA TCGAAGGCGA CGCGGGGAGC CCATCCCAGC TCCTCGGTGA 13741 TCTTCCGGGT GTCCACGCAG TAGCGACGGT CGTGCGCGGC CCGGTCCGGC ACCCGGTCCA 13801 CCACGGACCA GTCGGCACCG AAGACGCCGA GAAGACGACG GGTGAGGTCG ACGTTGGACA 13861 GTTCCGTCCC GCCGCCGATG TTGTACACCT CTCCGGCCCG CCCCCGGGCG GCGACCATGG 13921 CGATGCCCCG GCAGTGGTCG TCCACGTGCA GCCAGTCGCG CCGGTGGAGG CCGTCCCCGT 13981 ACAGGGGAAG GCGCAGGCCC TCCAGCAGAT GGGTCACGAA GAGCGGGACG ACCTTCTCGG 14041 GGTGCTGGTG GGGGCCGTAG TTGTTGGAGC AGCGCGTCAC CCGGACGTCG AGGCCGTGGG 14101 TACGGTGGAA GGCGAGCGCC AGGAGGTCGG AGGAGGCCTT GGACGCCGCG TAGGGGGAGT 14161 TCGGGTCCAG CGGATCGGCC TCGGTGGAGG AGCCCTCGGG GATCGATCCG TACACCTCGT 14221 CGGTGGAGAC GTGGACGAAG CGGCTGACGC CCGCTTCGAG CGCCGACCGC AGCAGGGTCT 14281 GCGTCCCCAG CACGTTGGTG GTGACGAAGG CGGCGGAGTC CGTGATCGAG CGGTCCACGT 14341 GCGACTCGGC GGCGAAGTGC ACCACCAGGT CGGTGCCGCG CAGGGCCTGG GCCACCGTGG 14401 GCGGGTCGCA GATGTCGCCG TGCAGGAAGG TGTGACGGGG GTGGCCGGCG ACCTCGGCGA 14461 GGTTCTCGGT GTTCCCGGCG TACGTGAGCT TGTCCAGCGA GAGGACGTGG GCGCCGGCCA 14521 GCTCCGGATA GGAGCCCGAC AGGAGCTGTC TGACGAAGTG CGAGCCGATG AAGCCCGCTG 14581 CCCCGGTCAC CAGGACGCGC ATCCTTGATC CGCCTTTCTG CCGTGCTGTG TGGGGGAGGT 14641 GTGGTCAACC GGTGCGCGTC GCCCCGAGTC CCGAGGCGAC CTCCATGAGG TAGTCCCCGT 14701 AGCTGGAGGC GCTCAGCTCC TCACCCAGCC GGTAACAGGT GTCCGCGTCG ATGAAGCCCA 14761 TGCGCAGCGC GATCTCCTCG AGACAGGCGA TGCGTACGCC CTGGCGCTGC TCGAGGAGCT 14821 GGACGTACTG ACCCGCCTGG AGCAGGGAGT CGTGGGTTCC CATGTCGAGC CAGGCGAATC 14881 CACGTCCGAG CTGGGTCAGC CGGGCGCGGC CCTGCTCCAG ATAGGACAGG TTGATGTCGG 14941 TGATCTCCAA CTCGCCTCGG GCTGAGGGCT TGAGGTCCTT CGCCAGCTCC ACCACGTCGT 15001 TGTCGTAGAA GTACAGCCCG GTGACGGCGA GGTTGGAGCG AGGACGGCTC GGCTTCTCCT 15061 CCAGGGACAA CAGGTGCCCC TGCTCGTCGA TCTCGGCGAC GCCGTAGCGC TCGGGCGACT 15121 TGGACGGATA GCCGAACAGT TCACATCCGT CGAGACGTCG CAGGGAGTGC TTCAGGACGG 15181 TGGAGAATCC GGGGCCGTGG AAGACGTTGT CGCCCAGAAT GAGCGCCACC CGGTCGTTCC 15241 CGATGTGCTT GTCGCCGACC AGGAACGCGT CGGCGACACC GCGCGGCTCG TCCTGGACCG 15301 CGTAGTCGAG CTGGATACCG AGGCGCGAGC CGTCGCCGAG CATGACCTGG AACGTCTCCA 15361 CGTGCTGGTG CGAGGAGATG ATGAGGATGT CCTGGATTCC CGCCAGCATC AGCACCGACA 15421 GCGGATAATA GATCATGGGT TTGTCATAAA CGGGCAACTG CTGTTTGGAA AGCGCACCGG 15481 TCAGCGGCTG CAGTCGAGTG GCGCTTCCCC CGGCGAGGAT TATCCCCCTC ACTCCGGGGC 15541 GTTTCAGCGG TGTCTCGAAC ACGGTTGGTC CTCCGTGGTC ACATGGCCGA TATGGGGGGT 15601 GAAGACACTG TCCTGAGAGG CCGGCGGACC GGCTGTCGCC TCGCGGACAC AGCGGCTTAA 15661 TGCATTCACC CCGCCCCGGG ACCGTCATCC GAGAAGAAGG AATGCGGTGT CGTGGGAACC 15721 GACGTCCAGG AGTTCCTTTC GGGCCGCGGA ACGGCGGCGC GGAGATTCTG AACCGCGGGG 15781 GATTCCAGGG CGGTGGCAGG GAAGGGAACC ACCGCCGCGC CATCTCTCCC GGAACGTTCC 15841 GCAAGCGGCG GGCCGTGCTT CGGACGGCCT ATCTCTGCGC CTGTTGCTGT TCCTGCCAGG 15901 CCTGATAGGT CGGCAGCAGA CCGAGCCGTT CGGCCGTCGC GAGGGTCGGG GCGTTCTCGT 15961 CCCTGTCGGA GAGCAGCGGC TCGATGTCGT CCGGCCACGC GATTCCGAGG TCGGGGTCGA 16021 GCGGATTGAC GGAGTGCTCG CGTGCGGGAG CGTATCCGGA GGAGCAGAGG TAGACGAGCG 16081 TGGCGTCGTC GGTGAGGGAG AGGAAGGCAC GGCCCAGTCC CGCGGTCAGA TAGACGGCGG 16141 TGTTGCGTTC CGCGTCCATG GGCACGATCT CCCAGCGCCC GAAGGTCGGC GAACCGATGC 16201 GGACGTCCAC GACGACGTCG AGGCCGGCTC CCCGCACGCA CACGCTGTAC TTGGCCTGAC 16261 CTGGCGGGAT CTCGGTGTAG TGGATCCCGC GCAGCGCGCC GCGGTGCGAC ACCGCGACAT 16321 TGACCTGGGC CACCGGGAAG TCATGGCCGA ACGCCTGACG GAAGCTCTCG CCCCGGAACC 16381 ACTCGTGGGA CCTCCCGCGG TGGTCGGAGT GGATGACGGG TTCCTGCGAC CAGGCCCCCT 16441 CGATGCTGAG TGGATGCATC GCGCCTTCTC CTTCGGACCG ATGGGTGGGG TGCGGGGCGG 16501 GCCGGGGGCA CGGCCGAGCC GGTCAGCTGG AGCGTCTCCA GTAGGAACCC TGGCGATCGA 16561 TCTGGTGGAT CTCGTCCGTG ATGCCGTGCT CGTCCCGGAA CTCGTGGACG GCCTGCCGGC 16621 ACGCCGGAAT GCAGTAGTCG TCGACGATGA CGTACCCGCC GTCCGACACC TTGTGGTAGA 16681 GGTTGGTGAG AACCTCCCTG GTGGCTGCGT ACGAGTCCCC GTCGAGCCTC AGCACCGCGA 16741 GCCTCTCGAT GGGCGCGGTG GGCATCGTGT CCTTGAACCA GCCCGGGAGG AAGCGGACCT 16801 GGTCGTCCAG GAGTCCGTAG CGCGCGAAGT TCCCCTTCAC GGTCTCCACG TCGACCGGGA 16861 TGCTGAGGAC GTCGTTGTAC TGGCCGAGGT CGATGTCGAC GTCCAGCTGG TGGTCGTCCT 16921 CGGTGGTCTT GGGGAAACCC TGGAAGGAGT CCGCGACCCA CACCTTCCGG TCCCGCACGC 16981 CGTGCGCCCG GAAGACGCCG CGGGCGAAGA TGCAGGCCCC GCCCCGCCAG ACCCCGGTCT 17041 CCGCGAAGTC CCCCGGCACG CCGTCGCGCA GCACGTCCTC CAGGCACTTC TGCAGGTTGT 17101 CGAGCCGCTT GAGACCGACC ATCGAGTGCG CCACGCGCGG AAAGTCCTCA CCCACCGAGC 17161 GCAGTTCCGC GGAATACGAG CTGCTGGTGA TGAGGCCGGC GACATTGGTC TGGTCCTCGT 17221 AAATCATGTT CGTCACGACC TTCTTCAGAA GGTCGAGATA CAGGTCCGCT TCGGCAGCTA 17281 TGACAGTCAT TTTCCTCACT TACGGGTAGC AGTGCCCAGC GGGCGGCTCG TTCAGGACGG 17341 GGGCCGCCGG GGCTGAATTC CCTGTGTCCA CACAGATGAG GTGGATGAGG TGGATGAGGT 17401 AGCCATCTAA CCCCAGTGAT CAGATTCGGG CAAGGGTCGA AAACGAGCCA CGTCTTATGT 17461 CGATCCTGTC CGGAAGCGAG GGGCATATGG TGCAGTGGCG ACTGCGGCCG ATCTGGCTGA 17521 TCCTTGCTGC GGCGCTGACC GTGTGCTTGC ATGTTGGACG TAGATCACCT TCTCCCGATT 17581 GCATTCAGGG TGAGGAAATC CATGAAATCT TCAAAAGTCG TTCACAGCCG TCCTGCGGAA 17641 GCGGGCGTCG CATGGCCCGT CGCGCGAACC TGCCCCTTTA CGCTCCCTGA TCAGTACGCA 17701 GAGAAGCGCA AGAACGAGCC CATATGCCGG GCTCAGGTCT GGGACGACTC CAGAACCTGG 17761 CTCATCACCA AGCACGAGCA CGTACGAGCC CTTCTCGCCG ACCCCCGGGT CACCGTCGAC 17821 CCGGCCAAGC TGCCCAGGCT CTCCCCCTCC GACGGCGACG GCGGCGGCTT CCGGTCCCTG 17881 CTGACCATGG ACCCCCCGGA CCACAACGCC CTCCGCCGCA TGCTCATATC CGAGTTCAGC 17941 GTGCACCGGG TCCGGGAGAT GCGCCCGGGC ATCGAGCGCA CCGTGCACGG GCTGCTGGAC 18001 GGGATCCTCG AACGGCGGGG GCCGGTGGAC CTGGTGGCCG AACTCGCGCT GCCGATGTCC 18061 ACCCTGGTGA TCTGTCAGCT CCTCGGAGTG CCCTACGAAG ACCGCGAGTT CTTCCAGGAA 18121 CGCAGCGAAC AGGCCACCCG GGTGGGCGGG AGCCAGGAAT CGCTGACCGC GCTCCTGGAA 18181 CTACGGGACT ACCTGGACCG GTTGGTCACC GCGAAGATCG AGACGCCGGG TGACGACCTG 18241 CTGTGCCGGC TCATCGCCAG TCGACTGCAC ACCGGTGAGA TGCGACACGC CGAGATCGTG 18301 GACAACGCCG TGCTGCTGCT CGCCGCCGGC CACGAGACCA GTGCCGCCAT GGTGGCACTG 18361 GGCATCCTGA CACTGTTGCG GCACCCCGGC GCCCTGGCGG AGTTGCGGGG CGACGGTACG 18421 CTGATGCCGC AGACGGTCGA CGAACTCCTG CGTTTCCACT CCATCGCGGA CGGCCTTCGA 18481 CGGGCGGTCA CGGAGGACAT CGAACTCGGC GGCATCACGC TGCGCGCCCC AGACGGCCTC 18541 ATCGTCTCGC TGGCCTCCGC CAACCGCGAC GAGAGCGCCT TCGCCTCCCC GGACGGCTTC 18601 GACCCGCACC ATCCGGCGAG CCGGCACGTC GCCTTCGGCT ACGGCCCCCA CCAGTGCCTG 18661 GGCCAGAACC TGGCCCGGCT GGAGCTGGAG GTCACCCTGG GCGCGGTGGT GGAGCGCATT 18721 CCCACGCTCA GGCTGGCCGG CGACGCCGAC GCACTGCGCG TCAAACAGGA TTCGACCATC 18781 TTCGGGCTGC ACGAGCTGCC GGTCGAGTGG TGACGGAAGG AGGACACAGC GTGCGGGTGA 18841 CAGTCGACCA GAGCCGGTGC CTGGGAGCCG GCCAGTGCGA GCAGCTGGCG CCGGAGGTCT 18901 TCCGCCAGGA CGAGGAAGGA CTGAGCCGGG TCCTCGTCCC CGAGCCCGAT CCGGCGTCAT 18961 GGCCGCGGGT GCTCCAGACG GTGGACCTCT GCCCCGTACA GGCCGTCCTC ATCGACGAGG 19021 GCCCCGGTCC CGCGCCGCAG GACACCAAGT GACCGCTGAC CGCTGGGCCG GCCGCACGGT 19081 GCTCGTCACG GGAGCACTCG GGTTCATCGG CTCCCACTTC GTCCGACAGC TGGAGGCGCG 19141 CGGAGCCGAG GTGCTCGCCC TCTACCGCAC CGAACGGCCG CAATTACAGG CCGAGTTGGC 19201 CGCGCTCGAC CGAGTACGCC TGATCAGGAC GGAGCTGCGG GACGAGTCGG ACGTGCGAGG 19261 GGCCTTCAAG TACCTGGCAC CCTCCATCGA CACCGTCGTC CACTGCGCGG CCATGGACGG 19321 CAACGCGCAG TTCAAGCTGG AGCGCTCGGC CGAGATCCTC GACAGCAACC AGCGGACCAT 19381 CTCCCACCTG CTGAACTGCG TACGGGACTT CGGCGTCGGC GAGGCCGTGG TCATGAGCTC 19441 CTCCGAGCTG TACTGCGCGC CGCCCACCGC GGCGGCCCAC GAGGACGACG ACTTCCGCCG 19501 ATCCATGCGG TACACGGACA ACGGCTACGT CCTGTCCAAG ACCTACGGCG AGATCCTGGC 19561 CAGGCTCCAC CGCGAGCAGT TCGGCACCAA CGTCTTCCTG GTGCGACCGG GCAACGTCTA 19621 CGGGCCGGGA GACGGCTACG ACCCCTCCCG GGGCCGGGTG ATCCCCAGCA TGCTGGCCAA 19681 GGCCGACGCC GGCGAGGAGA TAGAGATCTG GGGGGACGGC AGTCAGACCC GGTCCTTCAT 19741 CCACGTCACC GACCTGGTAC GGGCCTCACT GCGCCTGCTG GAGACCGGCA AGTACCCCGA 19801 GATGAACGTG GCCGGCGCGG AACAGGTCTC CATCCTGGAG CTCGCCCGGA TGGTGATGGC 19861 CGTCCTGGGA CGGCCCGAGC GCATCCGCCT CGACCCCGGC CGCCCCGTCG GCGCCCCGAG 19921 CAGACTTCTG GATCTGACCA GGATGTCGGA AGTGATCGAC TTCGAGCCCC AGCCCCTGCG 19981 GACCGGGCTG GAAGAGACCG CTCGCTGGTT CCGCCACCAC ACGCGCTGAA CCTCCTCTCA 20041 TACCCCCCTG GAAGGTAACT CGTGGTCACA CACGCCCCGA ACTCGCTGAT CAGTGACATA 20101 ATCCGCGCCT CCGGCGGGCA TGACGCCGAC CTCAAGGACC TGGCCGCCCG ACACGATCCG 20161 GCCGACATCG TCCGCGTACT CCTGGACGAG ATCACCTCAC GCTGCCCCGC TCCCGTGAAC 20221 GACGTCCCCG TCCTCGTCGA GCTGGCCGTC CGGGCGGGAG ACCGCCTCTT CCCCACCTAT 20281 CTGTACGTCC TCAAGGGCGG CCCGGTGCGC CTCGCGGCCA AGGACGAGGC GTTCGTCGCC 20341 ATGCGCGTCG AGTACGAGCT GGGCGAACTG GCCCGCGAGC TGTTCGGACC GGTGCGGGAG 20401 AACGTCACCG GCGTCCGCGG AACGACTCTC TTCCCCTACG TCGGGGACAC GGCGTCGGAA 20461 GGCGAGGAGG ACTCGGGTGC CGAGCACATC GGCACGCACT TCCTGGCCGC GCAGCAGGGC 20521 TCCCAGACCG TGCTCGCCGG CTGCCATTCC CACAAGCCGG ACCTCAGCGA GCTCTCCTCG 20581 CGCTACCTCA CCCCGAAGTG GGGCTCGCTG CACTGGTTCA CCCCCCACTA CGACCGCCAC 20641 TTCAGGAGCT ACCGGGACCA GCCCGTACGC GTTCTGGAGA TCGGCATCGG CGGCTACAAG 20701 CACCCCGAGT GGGGCGGCGG CTCCCTGCGC ATGTGGAAGC ACTTCTTCCA TCGCGGCGAG 20761 ATCTACGGCC TGGACATCGT CGACAAGTCG CACTTCGACG CGCCGCGCAT CACGACCCTG 20821 CGCGGCGACC AGAGCGACCC CGACCACCTG CGGTCGATCG CCGAGAAGTA CGGACCGTTC 20881 GACATCGTCA TCGACGACGG AAGCCACATC AACGACCACA TCCGGACCTC GTTCCAGGCA 20941 CTGTTCCCGC ATGTGCGGCC CGGCGGCCTC TACGTGATCG AGGACCTGTG GACCGCCTAC 21001 TGGTCCGGCT TCGGCGGCGA CGAGGACCCG AAGCGGTACA GCGGGACGAG CCTGGGCCTG 21061 CTCAAGTCCC TCGTCGACTC GATCCAGCAC GAGGAACTGC CGGAGGCCGG CGACCACCGT 21121 CCCAGTTACG CGGACCAGCA CGTGGTCGGC ATGCACCTCT ACCACAACCT GGCGTTCATC 21181 GAGAAGGGCA CCAACGCCGA GGGCGGCATC CCCCCGTGGA TCCCACGCGA CTTCGAGACC 21241 CTCGTCGCCG TCTCCTCCGG GGGCCACGCA TGAGGAGCCG TCGGCACCAG CCACCCGAAC 21301 ACACCCGACC GGACCGCAGG AGGCCCGCAT GCGCGTGACC CTGCTGAGCG TCGGATCCCG 21361 AGGCGACGTC CAGCCGTTCG TCGCCCTCGG CATCGGCCTC AAGGCCCGCG GCCACGACGT 21421 CACCCTGGCC GCCCCCGCCA CGCTGCGGCC ACTGGTCGAG CGCGCGGGAC TGACGTACAG 21481 GCTGTCCCCC GGGGATCCCG ACGGATTCTT CACCATGCCC GAGGTCGTCG AAGCGCTGCG 21541 GCGCGGCCCC TCGTTCAAGA ACATGCTCGC GGGGATGCCC GAGGCGCCCG AGAGCTACAC 21601 ACAGCAGGTC GTCGACGCGA TCCACGACGC CGCCGAGGGC GCCGACCTCA TAGTGAACGC 21661 GCCCCTCACC CTGGCCGCCG CGTACGGGCA CCCGCCCGCC CCGTGGGCCT CGGTGTCCTG 21721 GTGGCCCAAC AGCATGACCT CGGCCTTCCC GGCCGTCGAA TCCGGGCAGC GCCACCTCGG 21781 ACCGCTGACG TCCCTGTACA ACCGCTACAC CCATCGCAGG GCGGCACGCG ACGAGTGGGA 21841 GTGGCGACGC CCCGAGATCG ACGGCTACCG CCGACGCCTC GGCCTCCGGC CCTTCGGCGA 21901 CGAGTCCCCG TTCCTCCGAC TGGGGCACGA CCGCCCGTAC CTGTTCCCCT TCAGCCCCAG 21961 CGTGCTGCCC AAGCCGCGGG ACTGGCCGCG CCAGAGCCAC GTCACCGGCT ACTGGTTCTG 22021 GGACCAGCAC GGGGAGCCGC CCGCCGAGCT GGAGTCGTTC CTGGAGGACG GGGAGCCCCC 22081 GGTGGCGCTC ACCTTCGGCA GCACCTGGTC ACTCCACCGG CAGGAGGAGG CCCTCCAGGC 22141 CGCCCTCGAC GCCGTCCGTG GCGTCGGACG CCGACTGGTC ATGGTCGACG GACCGGACAG 22201 CGACCTGCCC GACGACGTGC TCCGCCTGCA CCAGGTGGAC TACGCCACCC TCTTCCCCAG 22261 GATGGCCGCG GTGATCCACC ACGGCGGCGC CGGCACGACC GCCGAGGTCC TCCGGGCCGG 22321 AGTGCCCCAG GTCATCGTGC CGGTCTTCGC CGATCACCCC TTCTGGGCGG CTCGACTGTC 22381 CAGAACAGGC GTCGCCGCCC GGCCGGTCCC CTTCGCCCGC TTCAGCCGAG AGGCACTGGC 22441 GCAGAGCGTC CGCCAGGCGG TCACCGATCC CGCGATGGCG GGCCGGGCCA GGCGACTGGG 22501 CGAACGGGTC TCCAAGGAAC GGGGAGTGGA CACCGCCTGC GACATCCTCG AGAAGTGGGC 22561 GGAGACGGCA CGCGCCACGG CCTGACACGG CCACCGGCGG GCGGGCCCGG AAGCCGCACG 22621 CCCGCCGGCC GACGGGTCCC GGGACCGCGC CGCTACGCCG ACAACCGGTA GGCGGAGAGC 22681 CGCACGGAGA GCGTGACCCG AGTCGGCGCC GGCAGCCGCT GGATCGTCTC CAGATCCCGC 22741 TGCGCGTCAC GGTGCCAGGC ATTGGGCCCC ATGCCGACCA GGTGCGCCAG AGCCTGGTGG 22801 TCGAGAGCCA TGGTCCGGGT CAACTCCTCC GTGGCGACGG CCGAGAAGTG CGGAGCGAGC 22861 TGCTCCGCGA GACGCGACTC CTTGCCTTCG TCCACCTGCA GCAGGCCGAG GGCGCCGATC 22921 ACCTCCCGCA GGTGATCGGG CAGAGGAGTG ACAACCAGGA GAACGCCACG GGGATGGAGA 22981 ACGCGATGCA GTTCAGGACC GTTGCGGGGA GCGAACGTGT TGATCACCAT GCCGGCTGCG 23041 GCATCCCGCA GCGGAAGCGT CTGCCAGGCG TCGGTCACCG CGGCCGCGAT CCGCGGATGC 23101 GCCTTCGCGG CACGCCGCAC GGCGTACTTG GAGATGTCCA GCAGCAGGCC CTGGGCATCG 23161 GGGAACGCTT CCATGACCCC GGCGTGATAG TGGCCCGTCC CCCCACCGAT GTCGACCACA 23221 CAGCCGGGCA CGGCCGGATC GGCCGTCCGC CGCGCCAGAT CGACCAGCGC ATCCATCACG 23281 GGGTCGTAGT GACCCGCCGA CAGGAATGCG TCCCGGGCCT CCACCATTTC CTTGGTGTCG 23341 GCCCGCAGCT TCGTCGCCCT GGGAAGCAGA TTCACATAAC CCTGCTTCGC GATGTCGAAG 23401 GAGTGTCCGG CGGGGCAGAA AAGTGCGCGG TCGCCCTGAG CCAGCGAAGC ACCGCAGTGC 23461 GGGCAGGCGA GGTAGCGCAC GATCCTGTTG AGCATGGGGC ACCGTTCCTT CGGGCGAGTC 23521 GGCAGACCGG CCAACCCTAA CGCAGGCGCC CGGCCGCCCA CCGCCCGGCG CAGGGCCGAC 23581 GAACCACCGT GACGTGCACC AGCCGCGCGT GAGAACTCCT CATGCGCGCA CCCTACGGAA 23641 ATCGGCAGGT CAACCGGCGA TTCCTGCGGG AATTCCGAGC GAAACGGCCT CACTGTGTTT 23701 CCCCGCTGCA TTTCCTCGCT GAATTCAGCG AATCCCGGCA GACGACCGGC TCTGCCGGCG 23761 TGACAGCCCC TATCGATCGA CCAGGAGTTT CGATGGCCCC GAAGAGTGGT GCGCAGCGTT 23821 CGAGCGACAT AGCCGTCGTC GGCATGTCCT GCCGCCTTCC GGGGGCACCG GGCATCGATG 23881 AGTTCTGGCA TCTGCTGACC ACCGGAGGCA GCGCGATCGA GCGTCGCGCC GACGGCACCT 23941 GGCGCGGCTC CCTGGACGGA GCCGCCGACT TCGACGCCGC CTTCTTCGAC ATGACCCCCC 24001 GCCAGGCCGC CGCCGCCGAC CCGCAGCAAC GACTCATGCT GGAACTCGGC TGGACGGCCC 24061 TGGAGAACGC CGGGATCGTC CCCGGCAGCC TCGCCGGCAC GGACACCGGC GTCTTCGTCG 24121 GCATCGCGGC CGACGACTAC GCGGCACTCC TGCACCGGTC CGCCACCCCC GTCAGCGGGC 24181 ACACCGCGAC GGGCCTGAGC CGGGGCATGG CCGCCAACCG CCTCTCCTAC CTCCTGGGCC 24241 TGCGCGGTCC CAGCCTCGCG GTGGACAGCG CGCAGTCCTC CTCGCTCGTC GCGGTCCACC 24301 TGGCCTGCGA GAGCCTGCGC CGCGGCGAGT CCGACCTCGC GATCGTCGGC GGCGTCAGCC 24361 TGATCCTCGC CGAGGACAGC ACGGCGGGCA TGGAGCTCAT GGGCGCGCTC TCGCCGGACG 24421 GCCGCTGCCA CACCTTCGAC GCACGCGCCA ACGGCTACGT ACGCGGTGAG GGCGGAGCCT 24481 GCGTCGTCCT CAAGCCCCTG GAGCGGGCAC TGGCCGACGG GGACCGCGTC CACTGCGTCG 24541 TCCGAGGAAG CGCGGTCAAC AACGACGGCG GCGGCTCCAC CCTGACCACC CCCCACCGCG 24601 AGGCCCAGGC CGCCGTCCTG CGGGCGGCGT ACGAACGGGC CGGGGTCGGC CCGGACCAGG 24661 TGTCCTACGT CGAACTGCAC GGTACGGGGA CGCCGGTCGG CGACCCCGTC GAGGCGGCGG 24721 CTCTCGGCGC GGTCCTCGGC ACGGCCCACG GCCGTAACGC CCCGCTGTCC GTGGGATCGG 24781 TCAAGACGAA CGTCGGCCAC CTGGAGGCGG CCGCGGGCCT CGTGGGATTC GTGAAGGCAG 24841 CCCTGTGCGT CCGCGAGGGC GTGGTGCCGC CGAGCCTGAA CCACGCGACG CCCAACCCTG 24901 CCATCCCCAT GGACCGGCTA AACCTGCGCG TACCCACGCG ACTGGAGCCC TGGCCGCACC 24961 CGGACGACCG AGCGACCGGC CGGCTGCGAC TGGCCGGCGT CTCGTCCTTC GGCATGGGTG 25021 GGACGAACGC GCATGTGGTG GTGGAGGAGG CGCCGCTTCC GGAGGCCGGG GAGCCGGTCG 25081 GGGCCGGTGT GCCTTTGGCT GTGGTGCCGG TGGTGGTGTC GGGTCGTTCT GCGGGTGCGG 25141 TGGCTGAACT GGCCTCCCGC TTGAACGAGT CGGTTCGTTC GGATCGGTTG GTGGATGTGG 25201 GGTTGTCGTC GGTGGTGTCG CGGTCGGTGT TCGAGCATCG GTCCGTGGTT CTGGCGGGGG 25261 ACTCTGCCGA GCTGAGTGCC GGTTTGGATG CTCTGGCCGC TGACGGAGTG TCTCCTGTCC 25321 TGGTGTCGGG TGTGGCGTCG GTCGGGGGTG GCCGGTCGGT CTTCGTGTTC CCGGGTGCGG 25381 GGGTGAAGTG GGCGGGGATG GCGCTCGGGT TGTGGGCGGA GTCTGCTGTG TTTGCGGAGT 25441 CGATGGCGCG GTGTGAGGCG GCGTTCGCCG GGTTGGTGGA GTGGCGTCTG GCGGATGTGC 25501 TGGGTGATGG GGCTGCGTTG GAGCGTGAGG ACGTGGTGCA GCCGGCGTCG TTCGCGGTGA 25561 TGGTGTCGTT GGCGGCGTTG TGGCGGTCGT TGGGTGTGGT GCCGGATGCG GTGGTGGGGC 25621 ATTCGCAGGG GGAGATCGCT GCTGCGGTGG TGGCGGGTGG TCTGTCGTTG GAGGACGGCG 25681 CGCGTGTGGT GGTGTTGCGT GCGCGGGTGG CTGAGGAGGT TTTGTCGGGT GGGGGGATTG 25741 CTTCGGTGCG TCTTTCGCGG GCCGAGGTGG AGGAGCGGTT GGCGGGTGGG GGTGGTGGGT 25801 TGAGTGTGGC GGTGGTGAAT GCGCCGTCGT CGACGGTGGT GGCGGGTGAG TTGGGGGATT 25861 TGGATCGGTT TGTTGCGGCG TGTGAGGCGG AGGGGGTGCG GGCGCGTCGG CTGGAGTTCG 25921 GGTATGCGTC GCATTCGAGG TTCGTGGAGC CGGTGCGTGA GCGGTTGTTG GAGGGGTTGG 25981 CCGATGTCCG TCCGGTGAGG GGGCGGATTC CGTTCTATTC GACGGTGGAG GCTGCGGAGT 26041 TCGATACGGC TGGTCTGGAT GCGGAGTACT GGTTCGGGAA TCTGCGTCGG CCGGTTCGCT 26101 TCCAGGAGAC GGTCGAGCGG CTGTTGGCGG ATGGTTTCCG GGTGTTCGTG GAGTGCGGCG 26161 CGCATCCGGT GCTGACCGGG GCGGTGCAGG AGACCGCGGA GACTGCGGGC CGGGAGATCT 26221 GCTCCGTCGG ATCCCTGCGT CGTGACGAGG GTGGACTGCG TCGCTTCCTG ACCTCTGCGG 26281 CGGAGGCGTT CGTCCAGGGG GTGGAGGTGT CCTGGCCGGT GCTGTTCGAC GGCACCGGCG 26341 CCCGGACGGT CGACCTGCCC ACCTACCCCT TCCAACGCCG GCACCACTGG GCACCCGACG 26401 GCTCCGCGTC GGCGGCGCCC ACACGGGACA TCCGACCGGA CGAGACCGCC GCGGTTCCAG 26461 CGGACACGAT GGACCTCGCG GGACAACTTC GCGCGGACGT GGCGTCGTTG CCCACCACCG 26521 AGCAGATCGC GCGGTTGCTC GACCAGGTAC GCGACGGTGT CGCCACGGTC CTCGGACTGG 26581 ACGCCCGGGA CGAGGTGCGC GCGGAGGCGA CGTTCAAGGA ACTGGGCGTC GAATCGCTGA 26641 CCGGCGTCGA GCTGAAGAAC CACCTCCGTG CCCGGACCGG ACTGCACGTC CCCACCTCGC 26701 TGATCTACGA CTGCCCGACT CCCCTCGCCG CCGCTCACTA CCTCCGCGAC GAGCTCTTGG 26761 GCCGACCCGC GGAGCAGGCC GTCGTCCCCG CCGGCATCCC GGTCGACGAA CCGATCGCGA 26821 TCGTGGGGAT GGGGTGCCGT CTGCCGGGTG GGGTGTCGTC GCCGGAGGGG TTGTGGGATC 26881 TGGTGGCGTC GGGGGTGGAT GCGGTTTCTC CGTTCCCCAC GGATCGGGGT TGGGATGTGG 26941 GGGGTCTGTT CGATCCGGAG CCGGGGGTGC CGGGGCGTTC GTATGTGCGT GAGGGCGGGT 27001 TCCTTCATGA GGCGGGGGAG TTCGACGCGG GGTTCTTCGG TATCTCTCCG CGTGAGGCGT 27061 TGGCGATGGA TCCGCAGCAG CGGTTGTTGC TGGAGACGTC GTGGGAGGCG TTGGAGCGGG 27121 CGGGCATCGA TCCGCACACG CTTCGCGGTT CACGGACCGG CGTCTACGCC GGAGTGATGG 27181 CCCAGGAATA CGGCCCCCGA CTCCACGAAG GCGCAGACGG ATACGAGGGC TATCTGCTGA 27241 CCGGATCCTC CAGCAGTGTC GCCTCGGGTC GTATCTCGTA CGTGCTGGGT CTGGAAGGGC 27301 CGGCGGTGAC GGTGGACACC GCGTGCTCGT CGTCGCTGGT CGCGCTGCAC CTGGCCGTGC 27361 GGGCGCTGCG CAGCGGTGAG TGCGACCTCG CCCTCGCCGG CGGCGCGACC GTCATGGCCG 27421 AACCCGGCAT GTTCGTGGAG TTCTCACGGC AGCGCGGGCT GTCTGCCCAC GGACGGTGCA 27481 AGGCGTACTC GGACTCGGCC GATGGCACGG GCTGGGCCGA GGGGGCGGGT GTGCTGCTCG 27541 TCGAGCGGTT GTCGGATGCG GTACGTCATG GGCGTCGGGT GCTGGCGGTC GTGCGTGGTT 27601 CCGCGGTCAA CCAGGACGGT GCGAGCAACG GACTGACGGC GCCGAACGGG CGGTCCCAGT 27661 CGCGTTTGAT CCGTCAGGCG TTGGCGGATG CGCGGTTGGG TGTGGCTGAT GTGGATGTGG 27721 TGGAGGGCCA CGGCACGGGG ACGCGTCTGG GTGATCCGAT CGAGGCGCAG GCGTTGTTGG 27781 CGACGTATGG GCAGCGGGAT GCGGGTCGGC CTCTGCGGCT TGGTTCGCTG AAGTCGAACG 27841 TGGGGCATAC GCAGGCGGCT GCCGGTGTGG CGGGCGTGAT CAAGATGGTC ATGGCGATGC 27901 GGCACGGTGT CCTGCCGAAG ACGCTGCACG TGGATGAGCC GACGGCGGAG GTGGACTGGT 27961 CGGCCGGCGC GGTGTCCCTG CTGAGGGAGC AGGAGGCGTG GCCGCGTGGC GAGCGTGTGC 28021 GGCGGGCCGG AGTCTCCTCG TTCGGCGTGA GTGGGACGAA CGCGCATGTG GTGGTCGAGG 28081 AGGCGCCGGT TCCGGAGGAC GGGGAGGCGA TCGAGGGCGG TGCGCCTTTG GCTGTGGTGC 28141 CGGTGGTGGT GTCGGGTCGT TCTGCGGGTG CGGTGGCGGA GCTGGCGGGC CGGGTCAGCG 28201 AGGTCGCTGG GTCTGGTCGG TTGGTGGATG TGGGGTTGTC GTCGGTGGTG TCGCGGTCGG 28261 TGTTCGAGCA CCGGTCCGTG GTGCTGGCGG GGGACTCTGC CGAGCTGAAT GCCGGTCTGG 28321 ATGCTCTGGC CGCTGACGGA GTGTCTCCTG TCCTGGTGTC GGGTGTGGCG TCGGGTGAGG 28381 GTGGCCGGTC GGTGTTCGTG TTCCCTGGTC AGGGGACGCA GTGGGCGGGG ATGGCGCTCG 28441 GGTTGTGGGC GGAGTCGGCG GTGTTCGCGG AGTCGATGGC GCGGTGTGAG GCGGCGTTCG 28501 CCGGGTTGGT GGAGTGGCGT CTGGCGGATG TGCTGGGTGA CGGGTCTGCG TTGGAGCGGG 28561 TCGATGTGGT GCAGCCGGCG TCGTTCGCGG TGATGGTGTC GCTGGCGGAG TTGTGGCGGT 28621 CGTTGGGTGT GGTGCCGGAT GCGGTGGTGG GGCATTCGCA GGGGGAGATC GCTGCTGCGG 28681 TGGTGGCGGG TGGTCTCTCG CTGGAGGATG GCGCGCGTGT GGTGGTGTTG CGTGCGCGGT 28741 TGATAGGCCG TGAGCTGGCC GGGCGCGGTG GGATGGCGTC GGTGGCGCTG CCCCTCGCGG 28801 TGGTGGAGGA GCGTCTGGCG GGGTGGGCGG GGCGTCTGGG TGTGGCGGTG GTCAACGGAC 28861 CCTCCGCCAC GGTCGTCGCG GGTGATGTGG ATGCGGTGGG GGAGTTTGTG ACCGCGTGCG 28921 AGGTGGAGGG GGTTCGGGCG CGTGTTCTGC CGGTGGACTA CGCCTCGCAC TCGGCGCACG 28981 TGGAGGACCT GAAAGCCGAG CTTGAACAGA TTCTGGCCGG CATCGGCCCG GTGACCGGTG 29041 GCATCCCGTT CTATTCGACG TCCGAAGCCG CGCAGATCGA CACGGCTGGT CTGGACGCGG 29101 GGTACTGGTT CGGGAATCTG CGTCGGCCGG TGCGGTTCCA GGAGACGGTC GAGCGGTTGC 29161 TGGCGGATGG TTTCCGGGTG TTCGTGGAGT GTGGCGCGCA TCCGGTGCTG ACGGGGGCGG 29221 TGCAGGAGAC CGCGGAATCC ACCGGTCGCC AGGTGTGTGC GGTCGGATCC CTGCGTCGTG 29281 ACGAGGGAGG TCTGCGCCGC TTCCTGACCT CTGCGGCGGA GGCGTTCGTC CAGGGGGTCG 29341 GGGTGTCCTG GCCGGCACTG TTCGACGGCA CCGGCGCCCG CACGGTCGAC CTGCCCACCT 29401 ATCCCTTCCA GCGTCGGCGT TACTGGCTGG AGTCACGTCC TCCTGCGGCG GTTGTTCCGT 29461 CGGGGGTCCA GGACGGATTG TCGTATGAGG TGGTGTGGAA GAGCCTGCCG GTACGGGAGT 29521 CGTCGCGTCT TGACGGCCGG TGGCTGCTCG TCGTGCCCGA AACCCTGGAC GCCGACGGCA 29581 CGCGGATCGC CCACGACCTC CAGCACGCCC TCACCACCCA CGGCGCCACG GTCTCCCGTG 29641 TGTCGGTCGA CGTGACGACG ATCGACCGCG CCGACCTGTC GGCGCGGCTC ACCACGAGCG 29701 CGGCCGAAGA CCAGGAACCG CTTGGGCGAG TGGTGTCCCT CCTGGGGTGG GCCGAGGGAG 29761 TACGGGCCCA TGGCCCGAAC GTACCGACTT CCGTCGCCGC CTCCCTGGCA CTCGTGCAGG 29821 CTGTCGGCGA TGCCGGGTTC GGTGTTCCGG TGTGGGCGGT GACGCGGGGT GCGGTGTCCG 29881 TGGTGCCTGG TGAGGTGCCG GAGACGGCGG GTGCGCAACT GTGGGCGCTC GGCCGGGTCG 29941 CCGGTCTCGA ACTTCCCGAC CGTTGGGGTG GTCTGATCGA TCTTCCGGCG GATGCCGATG 30001 CGCGTACGGC GGGGCTTGCG GTGCGGGCCC TGGCCGCCGG GATCGCCGAT GGTGAGGACC 30061 AGGTGGCGGT GCGCCCCTCG GGTGCCTACG GCCGGCGTGT AGTTCAGGCA GCCCACCGGG 30121 AGCCGTCGGG AGCGAAGACG GAGTGGCGAC CGCGTGGCAC CGTGCTCGTC ACCGGGGGAA 30181 TGGGCGCCAT CGGCACTCGG GTGGCCCGCT GGCTGGCCCG GAACGGAGCC GAACACCTGG 30241 TGCTGACCGG CCGCCGCGGT GCCGGGACCC CCGGCGCGGA CGAGCTGGCG GGAGAGCTGA 30301 GGGCGTCCGG AGTCCAGGTC ACGCTCGCCG CCTGCGACGT GTCCGATCGT GCCGCGCTGG 30361 CCGCGCTGCT CGACGCGCAT CCGCCGACCG CCGTCTTCCA CACGGCCGGT GTACTGAACG 30421 ACGGAACGGT CGACACGCTC ACTCCCGCTC ACCTGGACGG GGTCCTGAGC CCCAAGGCGA 30481 CGGCCGCCGT TCACCTGCAC GAGCTCACCG CCCACCTGGA CCTGGACGCC TTCGTCCTCT 30541 TCGCCTCCGT CACCGGCGTA TGGGGTAACG GCGGCCAGGC CGGGTACGCC ATGGCCAACG 30601 CGGCTCTGGA CGCGCTCGCC GAGCAGCGCC GTGCCGGCGG ACTTGCGGCG ACCTCCATCA 30661 GTTGGGGCCT CTGGGGTGGC GGCGGCATGG CCGAGGGTGA CGGCGAGGTG AGCCTCAACC 30721 GTCGTGGAAT CCGCGCTCTT GAGCCCGCCA CCGGCATCGA GGCGCTGCAG CGGACGCTCG 30781 ACCAGGGCGC CACCTGCCGC ACCGTCGTCG ACGTGGACTG GGGTCAGTTC GCTCCTCGTA 30841 CGGCGGCGCT GCGGCGCGGG CGGCTCTTCG CGGATCTGCC CGAGGTGCGG CGTGTCCTGG 30901 AGTCCGAGGG GGTTGCACGG GAGGACGCCG GAACCGTCGA GCCCGGCGCC GTGCTCGCCG 30961 AGCGCCTCGC ATCGCGCTCC GAGGCCGAAC AGCGACGCAT GCTCGTCGAG TTGGTACGAG 31021 CCGAAGCGGC TGCCGTCCTG CGTCACGACA CGACGGACCT CCTGGCGCCG CGCAGGTCGT 31081 TCAAGGACGC CGGGTTCGAC TCCTTGACCG CGCTGGAGCT CCGTAACCGG CTGAACACCG 31141 CCACCGGTGT CGTCCTTCCC GTCACCGTCG TCTTCGACCA CCCGAACCCC GGTGCACTGG 31201 CGGACTTCCT GTACGGCGAA GCACTGGGCC TGTCCGCGGC CAGGTCTTCC GCGAGCGATA 31261 CGGCCGACAC GACCCGCCCG GCCGCCGCCC CCGAAGAGCC GATCGCGATC GTCGGAATGG 31321 CCTGCCGCTA CCCGGGCGAG GCCCGTTCCC CCGAGGPACT GTGGAAGTTG CTCATCGACG 31381 AACGGGACGT CATCGGCCCC ATGCCCACGG ATCGGGGTTG GGATGTGGGG GGTCTGTTCG 31441 ATCCGGAGCC GGGGGTGCCG GGGCGTTCGT ATGTGCGTGA GGGCGGGTTC CTTCATGAGG 31501 CGGGGGAGTT CGACGCGGGG TTCTTCGGTA TTTCTCCGCG TGAGGCGTTG GCGATGGATC 31561 CGCAGCAGCG GTTGTTGCTG GAGACGTCGT GGGAGGCGTT GGAGCGGGCG GGCATCGATC 31621 CGCACACGCT CCGCGGCTCA CAGACCGGCG TCTACGCGGG GATGTTCCAC CAGGAGTACG 31681 CGACCCGGCT GCACGAGGCA CCCGTGGAGT TCGAAGGCCA CTTGCTGACG GGGACGTCCG 31741 GGAGTGTGGC TTCGGGTCGT ATCTCGTATG TGCTGGGTCT GGAGGGGCCG GCGGTGACGG 31801 TGGACACGGC GTGTTCGTCG TCGTTGGTGG CGCTGCATCT GGCGGTGCGG GCGTTGCGGA 31861 GTGGTGAGTG TGACCTTGCT CTTGCGGGTG GGGTGACGGT GATGGCGGAG CCGGGTGTGT 31921 TCGTGGAGTT CTCGCGGCAG CGGGGGTTGG CTGCGGACGG GCGGTGCAAG GCGTTCGCGG 31981 CTGCTGCCGA TGGCACGGGC TGGGCCGAGG GTGTGGGCGT GCTGGCGGTG GAGCGGTTGT 32041 CGGATGCGGT GCGTCATGGG CGTCGGGTGC TGGCGGTGGT GCGTGGCTCG GCGGTGAATC 32101 AGGACGGTGC GAGCAATGGG TTGACGGCTC CGAACGGTCC GTCGCAGCAG CGGGTGATTC 32161 GTCAGGCGTT GGCGGATGCG CGGTTGGGTG TGGCTGATGT GGATGTGGTG GAGGGGCATG 32221 GGACGGGGAC GCGTCTGGGT GATCCGATCG AGGCGCAGGC GTTGTTGGCG ACGTATGGGC 32281 AGCGGGATGC GGGTCGGCCT CTGCGGCTTG GTTCGCTGAA GTCGAATGTG GGGCATACGC 32341 AGGCGGCTGC CGGTGTGGCG GGCGTGATCA AGATGGTCAT GGCGATGCGG CACGGGGTCC 32401 TGCCGAAGAC GCTGCACGTC GATGAGGTCT CTCCGCACGT CGACTGGTCG GCGGGCGCGG 32461 TGTCCCTGCT GACGGAGCAG GAGCCGTGGC CCCGTGGTGA GCGCGTACGG CGGGCTGGTG 32521 TCTCCGCGTT CGGTGTGAGT GGGACGAACG CGCATGTGGT GGTGGAGGAG GCACCTGCTT 32581 CGGAGGCGCC GGTCGCGGTG GAGCCGGTGG AGCCGGGGGC TGTGGGGCTT CTTCCGGTGG 32641 TGCCCGTGGT GGTGTCGGGT CGTTCTGCGG GTGCGGTGGC TGAACTGGCC TCCCGCTTGA 32701 ACGAGTCGGT TCGTTCGGAT CGGTTGGTGG ATGTGGGGTT GTCGTCGGTG GTGTCGCGGT 32761 CGGTGTTCGA GCATCGGTCC GTGGTTCTGG CGGGGGACTC TGCCGAGCTG AGTGCCGGTT 32821 TGGATGCTCT GGCCGCTGAC GGAGTGTCTC CTGTCCTGGT GTCGGGTGTG GCGTCGGTCG 32881 GGGGTGGCCG GTCGGTGTTC GTGTTCCCGG GTGCGGGGGT GAAGTGGGCG GGGATGGCGC 32941 TCGGGTTGTG GGCGGAGTCT GCTGTGTTTG CGGAGTCGAT GGCGCGGTGT GAGGCGGCGT 33001 TCGCCGGGTT GGTGGAGTGG CGTCTGGCGG ATGTGCTGGG TGATGGGGCT GCGTTGGAGC 33061 GTGAGGACGT GGTGCAGCCG GCGTCGTTCG CGGTGATGGT GTCGTTGGCG GCGTTGTGGC 33121 GGTCGTTGGG TGTGGTGCCG GATGCGGTGG TGGGGCATTC GCAGGGGGAG ATCGCTGCTG 33181 CGGTGGTGGC GGGTGGTCTG TCGTTGGAGG ACGGGGCGCG TGTGGTGGTG TTGCGGGCGC 33241 GGGTGGCTGA GGAGGTTTTG TCGGGTGGGG GGATTGCTTC GGTGCGTCTT TCGCGGGCCG 33301 AGGTGGAGGA GCGGTTGGCG GGTGGGGGTG GTGGGTTGAG TGTGGCGGTG GTGAATGCGC 33361 CGTCGTCGAC GGTGGTGGCG GGTGAGTTGG GGGAGTTGGA TCGGTTTGTT GCGGCGTGTG 33421 AGGCGGAGGG GGTGCGGGCG CGTCGGCTGG AGTTCGGGTA TGCGTCGCAT TCGAGGTTCG 33481 TGGAGCCGGT GCGTGAGCGG TTGTTGGAGG GGTTGGCCGA TGTCCGTCCG GTGAGGGGGC 33541 GGATTCCGTT CTATTCGACG GTGGAGGCTG GGGAGTTCGA TACGGCTGGT CTGGATGCGG 33601 AGTACTGGTT CGGGAATCTG CGTCGGCCGG TTCGGTTCCA GGAGACGGTC GAGCGGTTGT 33661 TGGCGGATGG TTTCCGGGTG TTCGTGGAGT GTGGTGCGCA TCCGGTGCTG ACCGGGGCGG 33721 TGCAGGAGAC CGCGGAGACT GCGGGCCGGG AGGTGTGTGC GGTTGGTTCG CTGCGTCGTG 33781 ACGAGGGAGG TCTCCGTCGC TTCCTGACCT CTGCGGCGGA GGCGTTCGTC CAGGGGGTGG 33841 AGGTGTCCTG GCCGGTGCTG TTCGACGGCA CCGGCGCCCG CACGGTCGAC CTGCCCACCT 33901 ACCCCTTCCA ACGCCGCCAC TACTGGGCAC AGTCCTCGCC CGCCGGCGCC GGCAGCTCTG 33961 CTGCGGCCCG CTTCGGTATG ACCTGGGAGG AGCATCCGCT CCTCGGCGGC GCGCTGCCGC 34021 TCGCGGACTC CGGCGAGCTG CTGCTCGTCG GGAGGATCTC CCCGGCCTCC CACTCCTGGA 34081 TCGCCGACCA CACCGTGGCC GGGACCGCCC TGCTGCCCGG GACGGCCTTC GTCGACATGG 34141 CACTGCACGC CGCCGCGGTC GCGGGCTGTG CGGGTGTGGA GGAGCTGAGC ATCGAGGCCC 34201 CGCTGCCGGT GCACGGCGGG ATCCGGCTCC AGGTGGTGAT CGACGAGCCC GACTCCTCCG 34261 CGCGGCGCCG CGTGAGCGTG TTCGCGAGGC CGGAAGAGGA AGACGGGGAC GCCGGCCGCT 34321 GGACCCGACA CGCCACCGGC GTGCTGACCC CCGACGTCGC CCCCGAGCCG GGCCGGCCGC 34381 AGTGGTGCCG GCAGGCCTGG CCGCCGAGCG GCTCCGTCCG GGTGGAGGCG TCGGAGCTCT 34441 ACGACCGGTT CTCCGCGCTG GGATACGACT ACGGCGAGGT CTTCGCCGGG GTCGAGGCCG 34501 TCTGGCTGCG CGAGGGCGAG GCCTTCGCCG AGGTCCGCCT GCCCACGGGC GCGGCGCCCG 34561 ACGCCGAGCG GTTCGGGGTG CACCCCGGCC TCCTCGACGC GGCTCTGCAC CCCTGGCTGC 34621 TGGGCGACTT CCTGTCGCGG CCCGACGGCG GATCCGTACT GCTGCCGTTC GCGTGGCGCG 34681 GCATCACGCT CCACACGGCC GGTGCCGACG CGCTGCGGGT CCGTCTCGGA CCGGCCGGAG 34741 AAGGCGCTCT GTCGCTCGAA GCCGTCGACC TCTCCGGTGC CCCGGTGCTG TCGATGGACG 34801 CACTGGTGCT GCGTCCGCTC GCCCAGGACC GCCTGGCGGA ACTGGTCGGC GGCACGACCT 34861 CCACCCCGCT GTACCGCGTG GACTGGCAGC GGAGCCCGAT CGCGAGGACG GCGCCGTCGG 34921 CCACGGGGCT CTTCGGCTCC CTCCCGTCCG GTGCCGTCCG CCGCTGGGCG GTCGTCGGGC 34981 AGGGCGGTGT CGCCGCACGG TACGCGACGG CGGAACCCGG CACGGGGTGC GTCGGGGTCT 35041 TCCCCGACCT GGACGCACTG CGTACGACGC TGGACTCCGG AGCGGACGGC CCCGACATCG 35101 TCCTCGCCGA CTTCGGGGCC CGGCCAGGCG ACGCCGCGCC GCACGGGACG GATCCGGCCG 35161 ACGGCGCACG CGACACGGTC CGGCGGGGGC TCGCCCTCAT ACAGGGCTGG CTGTCCGACG 35221 AGCGCTTCGC CGCCGCGCGT CTCGCCGTGC TCACCGAGCA CGCCGTCGCC ACCGAGGCGG 35281 ACACCCGCCG GACGGACCTC GCGGGCTCGG CACTGTGGGG GCTGATGCGT TCGGCGCAGA 35341 CCGAGCACCC CGACCGCTTC GTCCTCGTCG ACCACGACGG GCAGGACGCC TCGTACCGGA 35401 CGCTGCCCAC CGCGCTCGAC AGCGAAATCC CGCAACTGGC GCTCCGAGCC GGGGAGACGC 35461 TGGCCCCCGA ACTGGCGGTC CTGCCGAGTC CGGCCGACGG GGGGCCCGCG ACAAGCGCGG 35521 CGTTCGATCC CGAAGGCACG GTACTCGTCA CCGGAGCCAC CGGCACCCTC GGCAGCCTGC 35581 TGGCCCGGCA CCTGGTCACG GCACACGGCG TACGGCATCT GCTGCTGCTC AGCCGCAGCG 35641 GACGCGAAGC CGCGGGGGCC GCCGAACTGG AGCGTGAACT CCGTCAACGG GGAGCCGAGT 35701 TCCAGCTCCT CTCCTGTGAC GCGACGGACC GGGCAGCGCT GAAGGAGGCC CTCGCCACCG 35761 TCCCCGCCGC CCACCCGCTG ACCGCGGTGA TCCACACGGC CGGCGTCCTC GACGACGGCG 35821 TCGTCGAGGC GCTGACCCCC GAACGGCTGG ACCGCGTGCT GCGCCCCAAG GCGGACGCCG 35881 CGCTGAACCT GCACGACCTG ACCGAGGGAA TGCCGCTGAA GGCGTTCGTC CTGTACTCCG 35941 GGGCGGTCGG ACTGCTGGGT GGAGCGGGCC AGGCCAACTA CGCGGCAGCC AACGCGTTCC 36001 TGGACGGCCT GGCCCAACAC CGGCACGCGC AAGGGCTGCC CGCGGTGTCC CTGGCATGGG 36061 GACTCTGGAG CGCCACCAGC ACGTTCACCG ACCATCTCGG CGAGGTGGAC CTGCGGCGCA 36121 TGGAGCGGTC CGGCATCACG CCGCTCACGG ACGAGCAGGG CCTTGACCTG TTCGACCGGG 36181 CCCTCGGCGC CGCGGTGGAC GCGCCGCAGC TCTGCGTGAT GGGGCTGGAC ACGGCGGCGC 36241 TGCGCCGGCA GGCGGCCGAG CACGGGCCGA CTTCGATGCC TCCTCTGCTG CGTACGCTGG 36301 CGGCGCCTCC CGTACGGCGC GGCGCGGGGC GCTCCGGCCG GGGCGGACGG GCGGCGTCCG 36361 CCACGGACGC GCCGAGCCGG GCGCAGGCCC TGCGCGAGCG ACTGACGGGC CTGGACGCGG 36421 CGGCACGGCG GGACGAACTC CTGGTCCTGT CGCAGGCGCA GTTGGCCGAT GTGCTGGGCT 36481 TCGCCGACAA GACCGCGGTG GACCCCGTTC GTTCCTTCCG CGAGATCGGT CTGGACTCGC 36541 TGACCGCCGT CGAGCTGCGC AACCGGCTCG GTGTCGTCAC CGGACTGCGG CTGCCGCCGG 36601 CGCTGGTCTT CGACCACCCC AACCTCGACG CGCTCGCGGC CCACCTGGCG GAGCTCCTCG 36661 CGGCTGAGGG CCGGGACGAC GCGGGCGCCG CGGCGCTCTC GGGAATCGAC GCCCTGGACC 36721 GGGCGGTCCG GGAGATGGCG GCCGACGACA CGCGCCGTGA CGCCGTCCGC CGACGCCTCG 36781 CGGAACTGCT GGCGGTGGTC GGCGACGCCC CGCGGGACGG CGGCCGCGCC CCACGGGCGG 36841 CCGCCGACGC GGGAGGCCGC GACGCTCAAG CGGACCCCGA CCTGCTGGGC CGGCTGGACT 36901 CCGCCTCCGA CGACGATCTG TTCGCGTTCA TCGAAGACCA GCTGTGAGCG GGACGCCGCG 36961 CGCGTTCCCC ACCCGTCCCT AAGCGCCGCA TCAGGCGCAC TCGCACCGAC ACGAGCACGC 37021 AGGCCAGGAG GGTCCGGTCG ATGACGGCCA ACGATGACAA GATCCGCGAC TACCTGAAGC 37081 GGGTCGTCGC CGAGCTGCAC AGCACGCGGC AACGGCTCAA CGCCTTGGAG CACGACGCCC 37141 GCGAGCCCAT CGCCATCGTG GGGATGAGCT GCCGGCTGCC CGGCGGGGTG ACCACCCCCG 37201 AGAGCCTGTG GAGGCTGGTC GACTCCGGCA CCGACGCCGC CTCGCCGTTC CCCGACGACC 37261 GGGGCTGGGA CCTGGACGCG CTCCACCATC CGGAGTCGGG AGCCGTCCAC TCCCGCGAGG 37321 GCGGATTCCT CCACGACAGC GCGGACTTCG ACGCGGAGTT CTTCGGCATC AGCCCGCGAG 37381 AGGCCCTGGC CATGGACCCG CAGCAGCGGC TGCTGCTGGA GACCGCCTGG GAGGTGTTCG 37441 AGCGCGCCGG CATCGACCCG GTCTCCGCCC GCGGCTCCCG CACGGGGGTG TACGCGGGCG 37501 TCATGTACCA CGACTACGGC GCCCGGCTGA ACGAGATCCC GCCGGGCCTC GAGGGCTACC 37561 TGGTCAACGG CAGCGCGGGC AGCATCGCCT CGGGCCGGGT GGCCTACACC CTCGGTCTGG 37621 AGGGCCCCGC CGTCACCGTC GACACGGCCT GCTCCTCGTC ACTGGTCGCC GTGCACCTGG 37681 CGGCACAGGC ACTGCGGCGG CGGGAGTGCG ACATGGCGCT CGCGGGCGGC GCGACCGTCC 37741 TGTCCACCCC CGACCTGTTC ATCGACTTCG CGCGACTCGG CGGCCTGGCC TCCGACGGGC 37801 GCTGCAAGGC GTTCTCCGAC GCCGCCGACG GCACCAGCTT CGCCGAGGGC GCCGGCCTGC 37861 TGCTCCTCAT GCGGCTGTCG GACGCGGTGG CCGAGGGCCA CACCGTCCTG GCGGTCGTCC 37921 GAGGCTCCGC CGTCAACCAG GACGGGGCGA GCAACGGCCT GACGGCCCCC AACGGCCTCG 37981 CCCAGCAACG CGTGATCCGC GAGGCGCTCG CCGACGCGGA CCTGGACCCC GACCAGATCG 38041 ACGCGGTGGA GGCGCACGGC ACCGGAACCA GGCTCGGCGA CCCCATCGAG GCGCAGGCCC 38101 TGCTGCACAC GTACGGCACG AGCCGCAGCC CCGAACGACC CCTGTGGCTC GGTTCGCTGA 38161 AGTCCAACAT CGGCCACACC CAGGCCGCCG CCGGAGTGGC CGGAGTCATC AAGACGGTGC 38221 TGGCGATGCG CCACGGACGG CTGCCCCGCA CACTGCACGT CACCCGCCCC TCCAGCCGGG 38281 TGGAATGGTC GGCGGGCGCG GTGGAACTGC TCACGCGGGC ACAGGACTGG CCCGGCCAGG 38341 GGAACGCCCC GCGCCGCGCC GGAGTGTCGT CCTTCGGTGC CAGCGGCACC AACGCACACC 38401 TGATCCTGGA AGGCGTCCCG GACGGCGACA TCACGGTCGC GGAGACCCGA CCGGCCACCG 38461 GCGGCGGCGC CTGGCCGCTC GCGGGCCGGA CCGAAGCGGC CCTGCGCGCA CAGGCCCGGC 38521 GGCTCCACGA CCACCTCGCC GCCCGCCCCC ACGTCTCACC CGCCGCGGTC GGGCGGACGC 38581 TGGTCCGCTC CCGCACGGCG TTCGAGCACC GGGCCGTCGT CCTCGGACAG GACACCGCCG 38641 ACCTCCTGAG CGGCCTCGCG GAGCTGGCGT CCGGCGGCGC TCACGGACCC GGCGTGATCA 38701 CCGGCCGGGC CGCGCGCGGC CGCCGTACCG CACTGCTCTT CACCGGACAG GGCAGCCAGC 38761 GGCCGGGTGC CGGACGGCAT CTCTACGAGC GGTACGAGGT GTTCGCCCGC GCCCTGGACG 38821 AGACGGCCGC GGCACTCGAC CGGCACCTCG ACCGCCCGCT GCGCGACGTG ATGTTCGCGG 38881 AGCCGGGCGG CGCGACGGCC GGACTCCTCG ACCGCACCGA GTACACCCAG CCCGCACTGT 38941 TCGCCCTGGA AGTCGCCCTC TTCCGACTGG TGACCGCCGG GGGCCTGCGC CCCGACGCAC 39001 TCCTCGGGCA CTCCGTCGGC GAACTGGCCG CCGCCCACGT CGCCGGAGTG TTCACCCTGC 39061 CCGACGCCGC CCGCCTGGTG ACGGCGCGAG GCCGACTGAT GGGCGAGCTG CCGGCCGGTG 39121 GCGCCATGAT GGCGATCCAG GCGAGCGGCC CGGAGATCGA GGAGACGATC ACGGCGCTCG 39181 CGGCCCACCG GTCGGCGCGC GTCGCCGTCG CCGCACTCAA CGGTCCCGAC GCCACCGTGA 39241 TCTCGGGCGA CGAGGACGTG GTCGCCGAAC TCGCCACGCT GTGGCGGGAG CGGGGCCGCC 39301 GCACCAGGGC GCTGCCCGTC AGCCACGCCT TCCACTCGCC GCACATGGAC GCCGCACTGG 39361 AACCGTTCGC CCGGATCGCG CGCGACGTCT CCTACGCCGA ACCGCGCATC CCGGTGGTCT 39421 CCAACCTGAC CGGCGGCATC GCGTCGGCCA CGACGCTGTG CGCCCCCGAG TACTGGGTGC 39481 GCCACGCGCG CGAGGCCGTG CGCTTCAGCG ACGGCTTCCG CGCCCTGCGC GACCAGGGGA 39541 TCGACACCTT CATCGAGCTC GGACCGGACG GCGTGCTGTC CGCCCTGGGC CGCGACTGCC 39601 TCCGCGAGGA GGAAGGAGAC GCCCCACGCC AGGACGGCTC GGCGGACCCC GACACGACCG 39661 GCTCCCGCGC CGACGGGGGG CGGCGACCCG TGCTGACGGT GCCGCTGCTG CGCCGGGACC 39721 GCGACGAGAC GACCACCTGC CTCGGGGCCC TGGCCACCGT CCACACCCAC GGCGTCCCCG 39781 TCGACCTCGC GGCCGTGCAC GGCGCCCCCG AGGGGCCCGC CGTCGAGCTC CCCACCTACG 39841 CCTTCCAACG CACGCGCTAC TGGCTGGACG CCCCGGCCCC CGCCGCCGGC CCCACCGCCA 39901 CCGGTCTGGA GGCGACGGAC CAGCCCCTGC TCCCGGCCGT CATCGACCTG CCCGACGGGG 39961 AAGGCACCGT ACGGACCGGA CTGCTCTCCC TGCGCACCCA TCCGTGGATC GCCGACCACC 40021 GCGTCCGCGA CCACGCCGTG GTGCCCGGAG CGGCCCTGCT GGACGTCGCC GCCTGGGCGG 40081 GCACCGAAGC GGGCTGCCCC CGGGTCGCCG AACTGACCTT CGCCACGCCC CTCGTCCTGC 40141 CCGAGAACGG AGAAGGAGTC CGACTGCGCG TGACGGTCAG CGGCCCCGAC GCGGAAGGCA 40201 TCCGTTCGCT ACGCATCGAC TCCCGGCCCG CCGACACGGT CCGTACCGCC GATGCCCCCT 40261 CCGACTGGAC CCGCCACGCG TCCGGCACCC TCGTCCCCGC ACCCGAGGAG GCCGGCGACG 40321 GCACCGGCGT GCCGACCGAA CTGCTCGGCG CCTGGCCCCC GGCCGACGCG ACCCCGGTCG 40381 CCCTCGACGC GGACGCCGTC GCGGCCGAGT ATCAGCGCCT CGCGGCCGGC GGCGTGACGT 40441 ACGGCCCCGC GTTCCGGGCA CTGCGCGCCG TCTGGCGCCG CGGCGCAGAG GTCTTCGCCG 40501 AGGTCCGGCT TCCCGGCCAG GCGGCCGCCG ACGCCTCGCG GTACGGCATG CACCCGGCCC 40561 TGCTGGACGC CCTGACGCAC GCCACCGGGT TCGGCGAGCG GTCCACCGAG GCCCGCGGCC 40621 TGGTCCCGTT CGCCTGGAGT GACGTCCGGA TCCACGTCCG CGGCGCCGAC TCCCTGCGCG 40681 TACGCATCGC GCCGGCCGGC CCCGACGCCG TGACCGTCGC CGCGGTCGAC CCGACGGGCC 40741 GCCCGGTCCT CGCCGCCCGC TCGCTCACGC TGCGCCCCCT GGCGGAGAGC CGGTTCCAGG 40801 ACCCGGAGGC GGACAGCACG CCGCTGTACC GACTGGAGTG GACACCGGCC CCCGGTTCCG 40861 TGACCGGGCA CGCCGGTCCA AGGCAGGCGG CAGCGGAGTG GGGCGTCCTC GGCGACCCGG 40921 TCCAGGCCCT CCTCGACGCC GTGCGCGACG GGGCGGAGGC ACCCGTGCGA ACCCATGACG 40981 ACCTGCTCGC GCTCGCGGCC TCCGACACGG CCCCGCCCGA CCATGTGCTG GCGCTGCTGG 41041 GCCACGACGG GGACGCTCTC GCCACGGGCG CCCACGACCT GGCCGCACGC GCCCTGGCCC 41101 TGGTACAGGG CTGGCTGACC CACGCCCGCT TCGCCGACGC GCGACTGGTC GTGCTGACGC 41161 AGGGGGCGGT GACGGCCGGC ACGAGCCCCG TCCACCCGGC CGCGGCCGCC GCCTGGGGGC 41221 TGCTGCGCAG CGCACAGTCC GAGCACCCGG GCCGCTTCGT CCTCGTCGAC GCGGACCCCG 41281 CCGACCCGGC CGCCTCGTAC CGTTCCCTGC CACGGGCCGT CGCCTCCGGG GCGTCCCAAC 41341 TCGCCCTGCG CGGCGCCGAG ATCCTCGTCC CCCGGCTCGC CCGGGGAACG GACCGACAGG 41401 CCACCGTGCC CGGACACCCC GGCGACGTCA CCGCACCGGA GACGACCGCT GCCCCCGAGC 41461 CGGCCCCGTC CGGCACCCCC TCCGGCCCCT GGCCCGdGGA CGGCACCGTG CTCGTCACGG 41521 GCGGAACCGG GACCCTGGGC AAGGCCGTGG CCCGGCACCT CGTGACCAAG CACGGTGTCC 41581 GGCACCTGAT CCTGGCCGGT CGGCGAGGCG CGGACACCCC CGGGGCGGCC GACCTGGCCA 41641 CCGAACTGAC CGGCCTGGGC GCCACCGTGA ACATCGTCCG CTGCGATGCC GCCGACCGCT 41701 CGGCGCTCGA AGGCGTCCTG GCCGCCGTCC CCGCCGCGCA CCCGCTCACC GCCGTCGTGC 41761 ACACCGCCGG AGTGCTCGAC GACGGCATCG TCACGGCGCA GACGCCCCGA CGCCTCTCGG 41821 CGGTCCTGCG CGCCAAGGCG GACGCGGTCA GCCACCTGCA CGAACTGACC CGCGACCTGG 41881 ACCTGTCCGC CTTCGTCCTC TTCTCATCGG CCGCCGGAAC CCTCGGCAGC CCCGGCCAGT 41941 CCGGCTACGC GGCCGCCAAC AGCTTCCTCG ACGCGTTCGC CGCCTGGCGG CGAGCGCAGG 42001 GCCTCCCCGC CGTGTCCCTG GCATGGGGAC TGTGGGGTGA CGGCGGTGAC GGTCGTGACG 42061 GCGGTGGCTC GGCGGCCGAC GGCATGGGAG CGAGCCTGGC CGCCGCCGAC CTGGCACGGC 42121 TGCGCCGTTC CGGCATCCTC CCGCTCGACC CGGCCGAAGC GCTGCGCCTG TTCGACGAGG 42181 CCTGCGACCC CGCCAGGACC GAGGCCGTAC TGCTGCCGAT CCGCCTCGAC CTGACCGGCC 42241 TGCGCGCCCG TTCCGCCCGC GGCGCCGTAC ACGCGAGCGT GGTGCCCGAA GTGCTGCACA 42301 CCTTGGTGCC CCCGCCCGCC GGTGCCGGAT CCCCGGCCGG TGCCGACGCG TCGGATCCCG 42361 CGGCGGGCCA GGCGCCCCCG GCCCCGGCGT CCGACACCCT GGCCGAACGG CTCGCCGGGA 42421 AGCCCCGAGG CGAACGGCTC ACCGCCCTCA CCCAACTGGT ACGCACCGAG ATCGCCTCGG 42481 TACTCGGGCA CCCCGACTCC GGCCGCGTCC AGCTCCAGTC CTCCTTCAAG GAGTCCGGCT 42541 TCGACTCGCT CACCGCCGTC GAACTCCGCA ACCGGCTCAC CGCGGCCACC GGAACGAAGC 42601 TTCCCGCCAC CCTCGTCTTC GACCATCCGA CACCCGCGGC ACTCGTCGAC CACCTGGAAC 42661 AGGAACTGCC GAAGGCAGCA CAGGAGATCC CGGCGGACCT CCCGGCCGTT CTCGACGCAC 42721 TCGACCGGAT CCGGGACGGA CTCGCCACCG CCGCCACCGA CGACAGCAGC CGCGACCACA 42781 TCGCGGAGCG TCTCCAGGCG TTGCTCGGCA CGCTCACCTC GGCTGCGGGC GTCAGCCGCC 42841 CGACCGGCAG CCCGGGCGAG CACGACCGGC AGGGCCCCGA TGAGCTGTCG CTCGGCCAAC 42901 GACTCGCCGC CAGCAGCGAC GACGAACTCT TCGACCTCTT CGACAGCGAC TTCCGATCGA 42961 CGTAGCCCAG GGCCACCCTT CCGCCTCCGC CGCCCGCCCC ACACCCCTGG AGAACAGCAC 43021 GATGTCTTCC ACATCGCCCG CCACCAACGA AGAGAAGCTC CGCGACTACC TCCGCCGCGC 43081 CATGACCGAC CTGCACGAGG CCCGCGAGCA GATCCGCCGG ACCGAGTCGG CCAGGCACGA 43141 GCCGATCGCG ATCGTGGGGA TGGGGTGCCG TCTGCCGGGT GGGGTGTCGT CGCCGGAGGG 43201 GTTGTGGGAT CTGGTGGCGT CGGGGGTGGA TGCGGTTTCT CCGTTCCCCA CGGATCGGGG 43261 TTGGGATGTG GGGGGTCTGT TCGATCCGGA GCCGGGGGTG CCGGGGCGTT CGTATGTGCG 43321 TGAGGGCGGG TTCCTTCATG AGGCGGGGGA GTTCGACGCG GGGTTCTTCG GTATCTCTCC 43381 GCGTGAGGCG TTGGCGATGG ATCCGCAGCA GCGGTTGCTG TTGGAGACGT CGTGGGAGGC 43441 GTTGGAGCGG GCGGGCATCG ATCCGCACAC GCTCCGCGGC TCACGGACCG GCGTCTACGC 43501 CGGAGTGATG TACCACGACT ACGGCAGCAC CGCGACCGTC TCCGTCGCCT CCGACGACGA 43561 GACCGCCGGA TTCCTCGGCA CGGGGACGTC CGGGAGTGTG GCTTCGGGTC GTATCTCGTA 43621 TGTGCTGGGG CTGGAGGGGC CGGCGGTGAC GGTGGACACG GCGTGTTCGT CGTCGTTGGT 43681 GGCGCTGCAT CTGGCGGTGC GGGCGCTGCG GAGTGGTGAG TGTGACCTTG CTCTTGCGGG 43741 TGGGGTGACG GTGATGGCGG AGCCGGGTGT GTTCGTGGAG TTCTCGCGGC AGCGGGGGTT 43801 GGCTGCGGAC GGGCGGTGCA AGGCGTTCGC GGCTGCTGCC GATGGCACGG GCTGGGCCGA 43861 GGGTGTGGGC GTGCTGGCGG TGGAGCGGTT GTCGGATGCG GTGCGTCACG GGCGCCGGGT 43921 CCTGGCGGTC GTGCGTGGTT CCGCGGTCAA CCAGGACGGT GCGAGCAATG GGTTGACGGC 43981 TCCGAACGGT CCGTCGCAGC AGCGGGTGAT TCGTCAGGCG TTGGCGGATG CGCGGTTGGG 44041 TGTGGCTGAT GTGGATGTGG TGGAGGGGCA TGGGACGGGG ACGCGTCTGG GTGATCCGAT 44101 CGAGGCGCAG GCGTTGTTGG CGACGTATGG GCAGCGGGAT GCGGGTCGGG CTTTGCGGCT 44161 TGGTTCGCTG AAGTCGAACG TGGGGCATAC GCAGGCGGCT GCCGGTGTGG CGGGCGTGAT 44221 CAAGATGGTC ATGGCGATGC GGCACGGTGT CCTGCCGAAG ACGCTGCACG TGGATGAGCC 44281 GACGGCGGAG GTGGACTGGT CGGCGGGCGC GGTGTCCCTG CTGAGGGAGC AGGAGGCGTG 44341 GCCTGAGGTG GGGCGTCTGC GTAGGGCTGC GGTGTCTTCG TTCGGTGTGA GTGGGACGAA 44401 CGCGCATGTG GTGGTGGAGG AGGCACCTGC TTCGGAGGCG CCGGTCGCGG GGGAGCCGGT 44461 GGAGCCGGTG GAGCCGGGGG CTGTGGGGCT TCTTCCGGTG GTGCCGGTGG TGGTGTCGGG 44521 TCGTTCTGCG GGTGCGGTGG CGGAGCTGGC CTCCCGCTTG AACGAGTCGG TTCGTTCGGA 44581 TCGGTTGGTG GATGTGGGGT TGTCGTCGGT GGTGTCGCGG TCGGTGTTCG AGCACCGGTC 44641 CGTGGTTCTG GCGGAGGACT CTGCCGAGCT GCATACCGGT CTGGTTGCTG TCGGGACTGG 44701 GGTGCCGTCG CCTGGCGTGG TGTCGGGTGT GGCGTCGGTC GAGGGTGGCC GGTCGGTGTT 44761 CGTGTTCCCT GGTCAGGGGA CGCAGTGGGC GGGGATGGCG CTCGGGTTGT GGGCGGAGTC 44821 GGCGGTGTTC GCGGAGTCGA TGGCGCGGTG TGAGGCGGCG TTCGCCGGGT TGGTGGACTG 44881 GCGTCTGGCG GATGTGCTGG GTGACAGGTC TGCGTTGGAG CGGGTCGATG TGGTGCAGCC 44941 GGCGTCGTTC GCGGTGATGG TGTCGCTGGC CGAGCTGTGG CGGTCGCTGG GTGTGGTGCC 45001 CGATGCGGTG GTGGGGCATT CGCAGGGGGA GATCGCTGCT GCGGTGGTGG CGGGTGGTCT 45061 CTCGCTGGAG GACGGCGCGC GTGTGGTGGT GTTGCGTGCG CGGTTGATAG GCCGTGAGCT 45121 GGCCGGGCAC GGTGGGATGG CGTCGGTGGC GCTGCCGGTC GCGGTGGTGG AGGAGCGTCT 45181 GGCGGCGTGG GCGGGGCGTC TGGGTGTGGC GGTGGTCAAC GCACCCTCCG CCACGGTCGT 45241 CGCGGGTGAT GTGGACGCGG TGGCGGAGTT TGTGACCGCG TGCGAGGTGG AGGGGGTTCG 45301 GGCGCGTGTT CTGCCGGTGG ACTACGCCTC GCACTCGGCG CACGTGGAGG AGCTGAGGGC 45361 CGAGCTTGAA CAGATTCTGG CCGGCATCGA CCCGGTGGCC GGTGAGACCC CCCTGTACTC 45421 CACGGTGGAG GCGGGTGTCG TGGATACGGC GTCGATGGAT GCGGGGTACT GGTTCAGGAA 45481 TCTGCGTCGG CCGGTTCGTT TCCAGGAGAC GGTCGAGCGG TTGCTGGCGG ATGGTTTCCG 45541 GGTGTTCGTG GAGTGCGGCG CGCATCCGGT GCTGACGGGG GCGGTGCAGG AGACCGCGGA 45601 ATCCACCGGT CGCCAGGTGT GTGCGGTCGG ATCCCTGCGT CGTGACGAGG GTGGTCTGCG 45661 ACGCTTCCTG ACCTCTGCGG CGGAGGCGTT CGTCCAGGGG GTGGAGGTGT CCTGGCCGGT 45721 GCTGTTCGAT GGCACCGGCG CCCGCACGGT CGACCTGCCC ACCTACCCCT TCCAGCGTCG 45781 GCGTTACTGG CTGGAGTCAC GTCCTCCTGC GGCGGTTGTT CCGTCGGGGG TCCAGGACGG 45841 ATTGTCGTAT GAGGTGGTGT GGAAGAGCCT GCCGGTACGG GAGTCGTCGC GTCTTGACGG 45901 CCGGTGGCTG CTCGTCGTGC CCGAAACCCT GGACGCCGAC GGCACGCGGA TCGCCCACGA 45961 CCTCCAGCAC GCCCTCACCA CCCACGGCGC CACCGTGCAC ACTCTTGCTC TTGACCCCAG 46021 CGCGGCGCAC TTCGACGGTC TCTTTGACGG GATACTCCAG GAAGAAACAG ATGTCACGGG 46081 CATCTTCTCT CTCCTCGGAC TGGCATCGGG CCCGCACCCG GATCACGGCG AGGTGGAGCT 46141 CGCGGGAGCC GCGTCGCTGA CGTTGATGCG CCAAGCCCAG CGAGACGGCT TCCGTGCTCC 46201 GGTGTGGGCG GTGACGCGGG GTGCGGTGTC CGTGGTGCCT GGTGAGGTGC CGGAGACCGC 46261 GGGTGCGCAA CTGTGGGCGC TCGGCCGGGT CGCCGGTCTC GAACTCCCCG ACCGTTGGGG 46321 TGGTCTGATC GATCTCCCGG CGGATGCCGA TGCGCGTACG GCGGGGCTTG CGGTGCGGGC 46381 CCTGGCCGCC GGGATCGCCG ATGGTGAGGA CCAGCTGGCG GTGCGCCCCT CAGGTGCCTA 46441 CGGCCGGCGC CTCGTACGAG CCACCGCGCG CCGGGGACGG AAGGACTGGC GCCCGCAGGG 46501 TACGGTGCTG CTCGCCGGGC ACCTCGACGC CGTCGGTGAA CCACTGGCCC GATGGCTGCT 46561 CACCGGCGGC GCGGACCACG TCGTCCTTGC GGATCCCGCC CTGACCGAAC TCCCGGCCAC 46621 CCTCGCGGAT CTGGCCCAGA CCGTGACGAC CGCTGCGGCA CCCGACCTTG CCGACCGTGC 46681 AGTCCTCGCC GCCCTGGTCA CCGAGTACGT ACCCGCCACC GTGGTCGTCG TTCCGCCCGC 46741 GGCGGAGCTC GCTCCGCTGG CGAGTATCAG CCCGGCCGAC CTCGCGGCGG CCGTCACCGC 46801 CAAGTCCGCG ACCGCGGCGC ACTTCGACGC GCTGCTCGAC GGACCCCACG CACCGGAGCT 46861 GGTGCTGATC TCCTCGGTCG CGGGGATCTG GGGTGGTGTC CGGCAGGGTG CGTACGCCGT 46921 CGGTGCCGCT CACCTCGATG CCCTGGCCGC CCGCCGCAGG GCCCGCGGTC TGTCGGCGGC 46981 CTCCGTCGCG TGGACGCCCT GGGCGGGTTC CGTCACCGCG GACGGCTCCG CCGCCGAGTC 47041 GCTGCGGCAG TACGGCATCG CTCCGCTGGA GCCGCAGGCG GCGCTCGCGG AGCTGGACCG 47101 GGCGCTGAAC CAGCAGCTGC ACGGCGGCGG GGGCGACGCG GCGGTGGCCG ACATCGACTG 47161 GGAGCGGTTC CTCGCGTCGT TCACCTCCGT ACGTCCCAGC GTTCTCTTCG ACGAGCTGCC 47221 CGAGGTACGC CGTCTCCGCG AGGCGGAGGC GGCGGCCATG GCGGACCAGG CCGCCGCCCG 47281 GACGGGAGCG CCCGGCGGAA CGGAGCTGGC GCGCTCTCTG CGGGCCAAGT CCCTGAACGC 47341 CCAGCGAACT GCGCTCCTGG AATTGGTCAC TGCCCACGTG GCGGCCGTGC TGGGAGAGAG 47401 CGTTCCCGAG GCGATCGACC GGAGCCGGGC GTTCAAGGAC ATCGGCTTCA CCTCCATGAC 47461 CGCGATGGAA CTGCGCAACC GGCTCAAGGA GGCCACCGGG CTCGCCCTTC CTGCCTCCCT 47521 CGTCTTCGAC CACCCCCACC CCGGCGCACT CGCCGACCAC CTGCGCGAGG AACTCCTGGG 47581 CGAGGACGGT GCGGCGGGCG CCGACTCCGC GGCGGAGGAA CCGAGCGCTA CCTCTCCGAC 47641 GGTCCAGGAC GAGCCGATCG CCATCATCGG CATGGCCTGC CGCCTCCCTG GTGACGTCGG 47701 AACACCCGAC GAACTCTGGG AGCTGCTGGA AACCGGCCGC GACGCGATGT CGGACCTGCC 47761 CGTCAACCGC GGGTGGGACG TGGCGGGGCT CTACGACCCG GATCCAGACG CGGCGGGGCG 47821 TTCCTACGTC CGGGAGGGCG GGTTCCTCCA CGACGCGGGG GAGTTCGACG CGGAGTTCTT 47881 CGGCATCTCG CCGCGTGAGG CGCTGGCGAT GGACCCGCAG CAGCGCATCG TCCTCGAACT 47941 CGCCTGGGAA TCGTTCGAAC GTGCGGGCCT GGACCCGGCC GGCCGCCGCG GCAGCCGTAC 48001 CGGCGTGTTC ATGGGAACCA ACGGCCAGCA CTACATGCCG CTGCTGCAGA ACGGCAACGA 48061 CAGCTTCGAC GGCTACCTCG GCACCGGGAA CTCGGCCAGT GTCATGTCGG GCCGCATCTC 48121 GTACACCCTC GGCTTGGAGG GGCCGGCGCT GACGGTGGAC ACGGCGTGTT CGTCGTCGCT 48181 GGTCGCGCTG CATCTGGCGG TGCGGGCGCT GCGCAACGGT GAGTGCGACC TCGCCCTCGC 48241 CGGCGGCGCG ACCGTGATGT CGACGCCGGA AGTCCTGGTG GAGTTCTCCC GGCAGCGTGC 48301 AGTCTCCGCA GACGGTCGCT GCAAGGCGTT CTCCGCCTCG GCCGACGGCT TCGGACCGGC 48361 CGAGGGTGCG GGCGTGTTGC TCGTCGAGCG GTTGTCGGAT GCGGTGCGTC ATGGGCGTCG 48421 GGTGTTGGCG GTCGTGCGTG GTTCGGCGGT GAATCAGGAC GGTGCGAGTA ATGGGTTGAC 48481 GGCTCCGAAC GGTCCGTCGC AGCAGCGGGT GATTCGTCAG GCGTTGGCGG ATGCGCGGTT 48541 GGGTGTGGCT GATGTGGATG TGGTGGAGGG GCATGGGACG GGGACGCGTC TGGGTGATCC 48601 GATCGAGGCG CAGGCGTTGT TGGCGACGTA TGGGCAGCGG GATGCGGGTC GGCCGTTGCG 48661 GCTTGGTTCG TTGAAGTCGA ACGTGGGGCA TACGCAGGCG GCTGCCGGTG TGGCGGGCGT 48721 GATCAAGATG GTCATGGCGA TGCGGCACGG TGTCCTGCCG AAGACGCTGC ACGTCGATGA 48781 GGTCTCTCCG CACGTCGACT GGTCGGCGGG TGCGGTGTCC CTGCTGACGG AGCAGGAGCC 48841 GTGGCCGGAG GTGGGGCGCC CTCGCAGGGC TGCGGTCTCT TCGTTCGGGC TCAGCGGGAC 48901 GAATGCGCAT GTGGTGGTCG AGGAGGCGCC GGTCGGGGAG GCGGGGCAGG CCGCCGGGGA 48961 TGCTCGGTTG GCTGTGGTGC CGGTGGTGGT GTCGGGCCGG TCTGCGGGTG CGGTTGCTGA 49021 ACTGGCCTCC CGCTTGAACG AGTCGATTCG TTCGGATCGG TTGGTGGATG TGGGGTTGTC 49081 GTCGGTGGTG TCGCGGTCGG TGTTCGAGCA CCGGTCCGTG CTACTGGCGG GGGACTCTGG 49141 CGAGCTGCAT ACCGGTCTGG TTGCTGTCGG GACTGGTGTG CCGTCGCCTG GTGTGGTGTC 49201 GGGTGTGGCG TCGGTCGGGG GTGGCCGGTC GGTGTTCGTG TTCCCTGGTC AGGGGACGCA 49261 GTGGGCGGGG ATGGCGCTCG GGTTGTGGGC GGAGTCGTCG GTGTTCGCGG ACTCGATGGC 49321 GCGGTGTGAG GCGGCGTTCG AGGGGTTGGT GGACTGGAGT CTGGCGGATG TGCTGGGTGA 49381 CGGGTCCGCG TTGGAGCGGG TCGATGTGGT GCAGCCGGCG TCGTTCGCGG TGATGGTGTC 49441 GCTTGCTGAG CTGTGGCGGT CGTTGGGTGT GGTGCCGGAT GCGGTGGTGG GGCATTCGCA 49501 GGGGGAGATC GCTGCTGCGG TGGTGGCGGG TGGTCTGTCG TTGGAAGACG GGGCGCGTGT 49561 GGTGGTGTTG CGTGCGCGGT TGATCGGCCG TGAGCTGGCC GGGCGCGGTG GGATGGCGTC 49621 GGTGGCGCTG CCGGTCGCGG TGGTGGAGGA GCGTCTGGCG GGGTGGGCGG GGCGTCTGGG 49681 TGTGGCGGTG GTCAACGGAC CGTCCGCCAC GGTCGTCGCG GGTGATGTGG ATGCGGTGGC 49741 GGAGTTTGTG ACCGCGTGCG AGGTGGAGGG GGTTCGGGCG CGTGTTCTGC CGGTGGACTA 49801 CGCCTCGCAC TCGGCGCACG TGGAGGACCT GAAGGCCGAG CTTGAAGAGG TGCTGGCCGG 49861 CATCGGCCCG GTGACCGGTG GGATCCCGTT CTATTCGACG TCCGAAGCCG CGCAGATCGA 49921 CACGGCTGGT CTGGACGCGG GGTACTGGTT CGGGAATCTG CGTCGGCCGG TGCGGTTCCA 49981 GGAGACGGTC GAGCGGTTGT TGGCGGATGG TTTCCGGGTG TTCGTGGAGT GTGGTGCGCA 50041 TCCGGTGCTG ACGGGGGCGG TGCAGGAGAC CGCGGAATCC ACCGGTCGCC AGGTGTGTGC 50101 GGTCGGATCC CTGCGTCGTG ACGAGGGAGG TCTGCGCCGC TTCCTCACCT CTGCGGCGGA 50161 GGCGTTCGTC CAGGGGGTCG GGGTGTTCTG GCCGGCACTG TTCGACGGCA CCGGCGCCCG 50221 TATCGTCGAC CTGCCCACCT ACCCCTTCCA ACGACGGCAC TACTGGTACA ACGACCCTGC 50281 CCGCCGCACG GGCGATGCCA CCTCCTTCGG TATGGCGCAG GCCGGTCATC CCTTGCTCGA 50341 TGCCGGTACG GAGCTCCCTG AATCAGGCGA GCACCTCTAC ACCGCTCGGC TCGCCGCCGA 50401 CTCGCATCCT TGGCTGCTGG AACACACCCT GCTGGGTGCG CCGTTGCTGC CCGGTGCGGC 50461 GTTCGTCGAC CTCGTCCTGT GGGCCGGCGG GGAGGTCGGA TGCGACCTGA TCGAAGAGCT 50521 GACGCTGACC TCGCCGCTGC TGTTGTCCGA CAGCGCTGCC CTTCAACTGC GGCTGGTCGT 50581 GGGCACGGCG GACGCCGAGG GACGTCGTAC GATCACCGTC CACTCGCGGC CGGACGGAGA 50641 CCCGCGTACG ACGCGCACAC CTGCGGCATC GTCCGAGACC AGCCCGGACG CGGAGTCGGA 50701 CACGGAGATC CGTAGGGACA CGTCCGCCTG GACGAAGCAC GCTCAGGCGA CGGTCGCCCC 50761 CGCCCCTGAC GTCCCCCCTT CCGGGGTGGA CGCGGAAGGG GACGCCGTTC GCCCCGCAGT 50821 GGAATGGAGC GTGGCGGCGA CGGAGTCGGA TGCCTTCCAG GCCGAGGACT TCTACGCGTC 50881 CTTCGCCGCA CACGGCTATG GCTACGGCCC GCTGTTCCAG GGCGTACGGT CAGGCCGTCA 50941 GGACGGGACC GACGTCTACG CCGAAGTCGC CCTGGATCAC GACCGCTTGC CGTCTGCCGA 51001 GCAGTTCGGC CTGCACCCCG CGCTGCTCGA CGCGGCGTTC CAGACGATGC GTCTGGGATC 51061 GTTCTTCCCC GACGACGGAC AGGCACGTGT GCCGTACACC TTCCGGGGGA TTCGTCTCTA 51121 CGCCCCGGGA GCCGCGCGCC TGCGGGTCCG TGTCTCGGCG GTCGGGGCCG ATGCCGTACG 51181 CGTGGAGTGC GCCGATGAGC GGGGGCGGCT CGTCTGTGAG ATCGACGCCC TCGTCGTCAG 51241 CACGGTCTCC CCGGACCAGT TGCGGCCGGC CGGACAGGAC GCGACCCAGG ACATGCTGCA 51301 CCGGATCGAG TGGCCCGTCC TCTCCCCGCC GACCGGCAGC GCCACCTCCC CTGCTCCGCC 51361 CCGCTGGATC GTGGTCGGGG GCGAGGACGA GGGCCTCGGG CTCGGGGGCC TTCGACTCGA 51421 CGGTCCGAGG CTTGACGGTC CCGGGCTTGC GGAAGCGCTG TCCGAAGCCG GTATGGGGAC 51481 CGAGCGTCAC CGGAACCTGG CCGACGCGCT GTCGGCCGTA CGGACGCCGG TGGACACGGC 51541 AGGCTCCGCT GCCGCCGCCG GCACGACCTC CCTCATAGCC GTCCCCGTAC CGCAGTCGCC 51601 CACCATGGAC GCCGGTGCCG TGCGCCACGC CGTCCACCGA GCCCTGGAGC TGGTGCAGGG 51661 CTGGGTGGCG GCGGACGAGG CGGCGGAAGA GGGCGGGAGC GACGGTGCCG CGGCCGACCG 51721 GCGGCTGGTG CTGGTCACGA GCGGAGCGGT GTCCACGGGT GACGCCGACC CGCTGCGCGA 51781 CCCGGTGGCC GCGGCCGTCT GGGGTCTGAT CAAGTCCGCC CAGTCGGAGC AGCCCGGCCG 51841 CATCGTCCTC GTTGACCTCG ACGAGGGAGC CGTGGACGGG GCGGCCTTGG CAGCCGCGAT 51901 CTCGACCGGC GAACCACAAC TCGCCCTGCG CGACGGCGAT GTGCACGTGC CCAGGCTGGC 51961 ACCCCTGTCC GTGCGGGACT CGCAGACGCT GCTGCCGCCC GCCGGTACGC GCGCCTGGCA 52021 TCTGGTCGGC GCCGGCACCG GAACCCTTTC GGACCTCGCG CTCGTACCGG CGCAGACCGA 52081 CACCGTCGCG CTCGCACCTG GGCAGGTGCG GATCGCGGTG CGAGCCGCCG GACTCAACTT 52141 CCGGGACACG CTCATCGCGC TCGGTATGTA TCCGGGCGAG GGCGTGATGG GCGCCGAGGG 52201 CGCCGGAGTG ATCACCGAGG TCGGCCCGGA CGTGGTGAGC CTCGCCGTCG GGGACCGCGT 52261 CCTGGGCATG TGGACCGACG GGTTCGGGCC GTACGTCGTG GCCGACCACC GCATGGTGGC 52321 CCCGATGCCG CGCGACTGGT CCTACGCGGA GGCCGCTTCG GTACCCGCCG TCTTCCTCAG 52381 TGCCTACTAC GGACTCAGGC ACCTGGCCGG TCTGCGCGCC GGCCAGTCGG TGCTGGTGCA 52441 CGCGGCGGCG GGCGGTGTGG GCATGGCTGC CGTCCAACTC GCCCGGCACT TCGGGGCCGA 52501 GGTCTTCGGC ACGGCCGGCA CGGCCAAATG GGACGCACTG CGGGCACAGG GCCTGGACGA 52561 CCGGCACATC GCCGGTTCAC GGACGCTGGA CTTCGCGGAC CGGTTTCTCG ACGCGACCGA 52621 GGGGCGCGGC GTGGACGTCG TCCTGAACTC GCTGGCGGGC GACTTCGTCG ACGCCTCCCT 52681 GCGACTGCTG CCGCGCGGAG GGCGGTTCGT GGAACTGGGC AACCCGGACG TACGCGACGC 52741 CGCGCAGGTC GCCGCCGACC GGCCGGGAAC CGTCTACCGG GCCTTCGAGC TGATGGAGGC 52801 CGGGCCGGAG CTGATCGGCC GCATGCTGAA CGAACTGCTG GAACTGTTCG AGTCCGGGGC 52861 GCTGCGCCTG CTGCCCGTCA CCCCGTACGA CATCCGGCGG GCACCCGACG CCTTCCGCAC 52921 GCTCAGCCAG GCCGGTCACG TCGGCAAACT GGTCCTGACG ATGCCACCGG CCTTCGAACC 52981 CCACGGCACG GTCCTGATCA CCGGCGGCAC CGGGAACCTG GGCGGAACAC TCGCCCGCCA 53041 TCTCGTGACC GAACACGGAG TGCGCCACCT GCTCCTGGCC GGACGTAGGG GGCCCGAGGC 53101 CGAAGGCGCC GCCGAACTCG TACGGGAACT GCACGACCTG GGCGCCTCCG TCACGGTCGC 53161 CGCCTGTGAC GTGGCCGACC GAGCGGCGCT CCGGAAACTC CTCGGCGGCA TACCGCCGGA 53221 GCGCCCGCTC ACCGGAGTCG TCCACGCGGC GGGCGTTCTC GACGACGGCG TGGTCACGTC 53281 ATTGACCCCG GACAGGGTCG ACGGCGTCCT GCGGCCCAAG GTGGATGCCG CTCTCAACCT 53341 CCACGAAGCG GCCCTCGATC CCGAACTCGG TCTCGACATC ACCGCGTTCG TCCTGTTCTC 53401 GTCCGTCGCT GCCCTGCTCG GCGGCTCGGG TCAGGGAAGC TACGCCGCCG CCAACGGCTT 53461 CCTCGACGGA CTCGCCCAGT ACCGGCGTGG CCGCTCGCTG CCCGCGCTCT CCCTCGGCTG 53521 GGGCCTGGCC GGGAGCGGCC GGATGACATC CCACCTGGAC AGCCGGGCCC TGCTCCGGCG 53581 CATGGCCAGG GGCGGTGTCC TGCCGCTGTC CCCGGCGGAG AGCATGGCAC TGTTCGACGC 53641 GGCCCAGGGC TTCGACGAGG CGCTCCAGGT GCCGGCGCGC TTCCACACCG CCGCACTGGG 53701 CGCCGACGGC AACGTCCCGC CGCTCTTCAA CGGACTGATC CGGGGCGGGA CGGCGCATGC 53761 CGAGGCCCGG CGCAGGACGG TCGGCGCGTC GCCCGCGGGT GGTCCTGCCG GAGGCGAGCC 53821 GGTGAACCTC GCCGACCGGC TGTCCGGACT GACGGAGGAC GAACAGCGGG CGCTGCTCCT 53881 CGACACGGTG CGCACGCACG CGGCTCTCGT CCTGGGCCAC ACGGGCACGG ACGGCATCCA 53941 GGCCGACCGG GCGTTCAAGG ACCTGGGATT CGACTCGCTG ACGGCCGTCG AGATGCGCAA 54001 CCGGCTCACC GCCGCCACGG GGCTGCACCT CGCGGCGACG CTGGTCTTCG ACCACCCCGC 54061 TCCGGCGGAC CTCGCCGAGC ACCTCCGCTC TCGACTCGTC CCCGAGGGGA CGGACGTACC 54121 GCCGCTCCTC GCGGAACTCG GTCGGCTCGA AACGGCGTTC AAGAAGCTGA CCACCGCGGA 54181 CCTCGCCTCG GTCGTGCCCG ACGACATCGC CCGCGACGAG ATCGCCGTAC GTCTCGCCGC 54241 CCTCGGTTCC CTGTGGAACG GGCTCCATGG CAACGGCCTC AGCGGAGACG CGGCGCAGAA 54301 GCACGGCGAC TCGATCGTCG AGGACATCGA CTCCGCCGAC GACGACGAGA TCTTCGCCTT 54361 CCTCGACGAG AGCTTCGGCG ACTCCTGACC GCAGGCACCT CCGTACGGAC CGACGACTCT 54421 GCAGACGGGT GATGAGAGAT GGCGACCGAA CACGAGCAGA AGCTCCGCGA CTACCTCAAG 54481 CGGGCCACCA CCGAACTCCA CAAGGCCACG GAACGGCTGA AGGAGGTCGA ACAACGCGCT 54541 CACGAGCCGG TTGCGATCGT GGGGATGGGA TGCCGGTTCC CGGGCGGGGC GTCCTCGCCT 54601 GAGGAGTTGT GGGACCTGGT GGCGGCGGAG ACGGACGCGG TCTCCCCCTT CCCGGTGGAC 54661 CGGGGGTGGG ACGTGACGGG GCTGTACGAC CCGGATCCGG ACGCGGCAGG GCGTGCCTAC 54721 GTCCGCGAGG GCGGGTTCCT CCACGACGCG GGGGAGTTCG ACGCGGGGTT CTTCGGAATC 54781 TCTCCGCGTG AGGCGTTGGC GATGGATCCG CAGCAGCGGT TGCTGCTGGA GACGTCGTGG 54841 GAGGCGTTGG AGCGGGCGGG CATCGATCCG CACACGCTGC GCGGCACGCG GACCGGGGTC 54901 TACATGGGTG CCTGGAACGG CGGATACGCC GAGGGGATTC CCCAACCCAC GGCGGAACTG 54961 GAGGCCCAGC TCCTCACCGG CGGCGTGGTG AGCTTCACCT CGGGCCGTGT GTCCTACCTC 55021 CTGGGTCTGG AGGGGCCGGC GGTGACGGTG GACACGGCGT GTTCGTCGTC GCTGGTCGCG 55081 CTGCACCTGG CGGTGCGGGC GCTGCGCAGT GGTGAGTGCG ACCTCGCCCT CGCCGGCGGC 55141 GCGACGGTGA TGTCGACGCC CGACGTGTTC GTGCGCTTCT CCCGGCAGCG AGGAGTGGCC 55201 GCGGACGGTC GCTGCAAGGC GTTCTCCGCG TCGGCCGACG GATTCGGACC GGCTGAGGGT 55261 GTGGGCGTGC TGGCGGTGGA GCGGTTGTCG GATGCGGTGC GTCATGGGCG TCGGGTGCTG 55321 GCGGTCGTGC GTGGTTCCGC GGTCAACCAG GACGGTGCGA GCAACGGACT GACGGCGCCG 55381 AGCGGACGAG CTCAGGCCCT TCTGATTCGT CGAGCGTTGG CGGATGCGCG GTTGGGTGTG 55441 GCTGATGTGG ATGTGGTGGA GGGGCATGGG ACGGGGACGC GTCTGGGTGA TCCGATCGAG 55501 GCGCAGGCGT TGTTGGCGAC GTATGGGCAG CGGGATGCGG GTCGGCCGTT GCGGCTTGGT 55561 TCGTTGAAGT CGAATGTGGG GCATACGCAG GCGGCTGCCG GTGTGGCGGG CGTGATCAAG 55621 ATGGTCATGG CGATGCGGCA CGGTGTCCTG CCGAAGACGC TGCACGTGGA TGAGCCGACG 55681 GCGGAGGTGG ACTGGTCGGc CGGCGCGGTG TCTTTGCTGA GGGAGCAGGA GGCGTGGCCT 55741 GAGGTGGGGC GTCTGCGTAG GGCTGCGGTG TCTTCGTTCG GTGTGAGTGG GACGAACGCG 55801 CATGTGGTGG TGGAGGAGGC GCCGGTTCCG GAGGACGGGG AGGCGGTCGG GGGCGGTGTG 55861 CCTTTGGCTG TGGTGCCGGT GGTGGTGTCG GGTCGTTCTG CGGGTGCGGT GGCGGAGCTG 55921 GCGGGCCGGG TCAGCGAGGT GGCTGCGTCT GGTCGGTTGG TGGATGTGGG GTTGTCGTCG 55981 GTGGTGTCGC GGTCGGTGTT CGAGCACCGG TCCGTGGTAC TGGCGGGGGA CTCTGCCGAG 56041 CTGAATGCCG GTTTGGATGC TGTGGCCGGT GGTGTGCCGT CGCCTGGTGT GGTGTCGGGT 56101 GTGGCGTCGG GTGAGGGTGG CCGGTCGGTG TTCGTGTTCC CTGGTCAGGG GACGCAGTGG 56161 GCGGGGATGG CGCTCGGGTT GTGGGCGGAG TCGTCGGTGT TCGCGGAGTC GATGGCGCGG 56221 TGTGAGGCGG CGTTCGTCGG CTTGGTGGAC TGGCGCTTGT CGCAGGTTTT GAGCGATGGG 56281 TCGGCGCTGG AGCGGGTGGA GGTGGTGCAG CCGGCGTCGT TCGCGGTGAT GGTGTCGCTT 56341 GCTGAGCTGT GGCGGTCGTT GGGTGTGGTG CCGGATGCGG TGGTGGGGCA TTCGCAGGGG 56401 GAGATCGCTG CTGCGGTGGT GGCGGGTGGT TTGTCGCTGG AGGACGGGGC GCGTGTGGTG 56461 GTGTTGCGTG CGCGGTTGAT CGGTCGTGAG CTGGCCGGGC GCGGTGGGAT GGCGTCGGTG 56521 GCGCTGCCGG TCGCGGTGGT GGAGGAGCGT CTGGCGGGGT GGGCGGGGCG TCTGGGTGTG 56581 GCGGTGGTCA ACGGACCGTC CGCCACGGTC GTCGCGGGTG ATGTGGATGC GGTGGCGGAG 56641 TTCGTGGCCG CGTGCGAGGT GGAGGGGGTT CGGGCGCGTG TTCTGCCGGT GGACTACGCC 56701 TCGCACTCGG CGCACGTGGA GGACCTGAAA GCCGAGCTTG AACAGATTCT GGCCGGCATC 56761 GGCCCGGTGA CCGGTGGGAT CCCGTTCTAT TCGACGTCCG AAGCCGCGCA GATCGACACG 56821 GCTGGTCTGG ACGCGGGGTA CTGGTTCGGG AATCTGCGTC GGCCGGTGCG GTTCCAGGAG 56881 ACGGTCGAGC GGTTGTTGGC GGATGGTTTC CGGGTGTTCG TGGAGTGTGG CGCGCATCCG 56941 GTGCTGACGG GGGCGGTGCA GGAGACCGCG GAATCCACCG GTCGCCAGGT GTGTGCGGTC 57001 GGATCCCTGC GTCGTGACGA GGGAGGTCTG CGCCGCTTCC TCACCTCGGC CGCGGAGGCA 57061 TTCGTCCAAG GCGTGGAGGT GTCCTGGCCG GCACTGTTCG AAGGCACCGG CGCCCGCACG 57121 GTCGACCTGC CCACCTACCC CTTCCAACGT CGGCGCTACT GGCTGGAGTC GCGCCCTCCC 57181 GCGGCGCCGA TCGAGACTGC CGCAGCCTCT GGCATCGAGA GCTGGCGCTA CCGCGTGGCG 57241 TGGAAGAGCC TGTCGCTGTC GGAGTCGTCG CGTCTTGACG GCCGGTGGCT GCTCGTCGTG 57301 CCCGAAACCC TGGACGCCGA CGGCACGCGG ATCGCCCACG ACATCCAGCA CGCCCTCACC 57361 ACCCACGGCG CCACGGTCTC CCGTCTGACG GTCGACGTGA CGACGACCGA CCGCGCCGAC 57421 CTGTCGGCGC GGCTCACCAC CACCGCGGCC GAAGACCAGG GGCCTCTCCG GGGCGTCCTC 57481 TCCCTCCTGT CCACCGATGA ACGGCAGCAC CCGGATCATC CCGGTGTCGA CCGTGCCACG 57541 GCGGGCACGA TGCTGCTCGC CCAGGCGTGC GGGGATCTGG TCGTGGCCCG GGGCGTGGAG 57601 CCGAGGCTGT GGGTCGTGAC CCGCGGGGCG GTCGCGGTGT CCCCCGCCGA GCGTCCGTCG 57661 TCAGCCGGCG CCCAGGTCTG GGGCCTGGGG CGCTGCGCGG CGCTCGAACT TCCCACTCGG 57721 TGGGGTGGGA TGGTCGACCT TCCCCCGGCG GCCCGGGATG CTGGAAGGCA CGTACGGCGG 57781 CTCGTGCGTC TGCTGTCGGA GACCTGTGCG GAGGACCAGG TGGCGCTGCG TGCGTCGGGT 57841 GCGTACGGCC GCAGGCTGCT GCCCGCGTCC AGCCCCTCCG TATCCGTCCC CCGGACCGCG 57901 AAGAGCGGCT ACCAGCCGCG CGGCACGGTG CTGGTGACCG GCGGAACCGG TGCCCTCGGT 57961 GGCCACTTGG CACGGTGGCT GGCCCGCAAC GGCGCCGAGC ACATCGTTCT GGCCGGGCGT 58021 CGGGGCGAGG GTGCTCCAGG AGCCGCGGAA CTGTCGGCGG AGCTCAAGGA GCTGGGTGCG 58081 GAGGTCACCG TCGCGGCCTG CGACGTGGCG GACCGGAACG CGTTGCGTGA CATGCTGGAA 58141 TCCCTGCCGG CCGACCGGCC GCTGTCGGGG GTGTTCCACG CTGCCGGTGT CCCGCACTCG 58201 GCGCCGCTGG CCGAGACGGA TGTGGCGGGG CTCGCCGCCG TGCTCCCGGG GAAGGTCGTC 58261 GGGGCACGGC ACCTGCACGA ACTCACCAGG GAGAAGGAAC TGGACGCGTT CGTGCTGTAC 58321 GCGTCGGGCG CCGGGGTGTG GGGGAGCGGC GGGCAGAGCG CGTACGGAGC CGCCAACGCC 58381 GCACTGGACG CGCTGGCCGA ACAGCGCCGG GCTGAGGGAC TGCCCGCCAC TTCGGTCTCC 58441 TGGGGCCTGT GGGACGGCGG AGGCATGGCC GGCGAGCGAG GCGAGGAGTT CCTCACCGCC 58501 CTCGGCCTGC GGGCCATGGA GCCCGAGTCG GCTGTCGCCG CCCTGGAGGA GGCCCTGGAT 58561 CGTGGGGACA CCTGCGTGAG CGTGGTCGAC GTCGACTGGT CCCGGTTCGC CGAGTCGTTC 58621 ACCGCCTTCC GGCCCAGCCC GCTGATCGGG GAGCTCCCCG GGGTACGTGC CGTGCCCGAC 58681 GGATCGGCGG GCGGACCGTC GGACGACCTC GCGGACGCTG CGCGGCACGG CGGGGCAGCC 58741 GACCGGGGTG TGCCTGCAGG GCTCGCCCGG GCGACGGGCG ACGACCGGCA GGACATCCTG 58801 CTCGATCTCG TACGCCGCCA TGCCGCCGCC GTCCTCGGTC ACCCGGGACC GCAGCACATC 58861 GAGCCCGACG CCGGTTTCCG GACCCTGGGG TTCAGTTCGG TCACCGCGGT GGAACTGGCC 58921 AACAAGCTCG GTGCGGCCGT GGGAACGAAG ATCCCCGCCA CCTTCGCGTT CGACCACCCC 58981 AACGCCCGTG CCGCGGCGTC CCGCCTCGAC GTCCTGTTGG CGGCGTCGAG CGATGAGACC 59041 GCGCAGGAGG CGGAGATCCG GCAGGCACTG CGGACTGTGC CGCTGGCCCG GCTGCGGGCT 59101 GCGGGGCTCC TCGACGGCCT GCTCGAACTC GCCGGGCTGG AAGCGGAGCC CGGCCTGCCG 59161 GGCGACGTAC CGGATCGCGG TGCGGCCACG CCGGACGAGG AGTCCGCCCT GGCGGAAGTC 59221 GACGGCCTGG ACGCCGAAGC ACTGGTCGAC CTCGTCCTCA ACCAGTCCGA CTCCTGACCG 59281 CCGGCGGCGG CGCCGCGGCC CGCCGTGCCG TCGCCGCCCT CGGCCGTACG AAGAACCCCA 59341 CAGACCTGAC CGGGTCACGG CCCGGTGCTC AGCAAGGAGA CCACTCATGG CTCTGTCCCA 59401 AGAGAAGGTA CTGGAGGCAC TGCGCACCTC CGTCAAGGAC GCCGAACGGC TGCGCAAGCG 59461 CAACCGCGAA CTCCTCGCGG CCCGCCACGA GCCCATCGCC GTCGTCGGCA TGGCCTGCCG 59521 CTATCCCGGC GGGGTCCGTT CGCCCGAGGA CCTCTGGGAA CTCGTCGTGT CGGGCACGGA 59581 CGCGGTGGGT CCCTTTCCCG AGGACCGTGG CTGGGACGTG GAGCGGATCT ACGACCAGGA 59641 CCCGTCCGTC CCGGGCACCA CGTACTGCCG CGAGGGCGGA TTCCTTTACG ATGCGGGGGA 59701 CTTCGACGCG GCTTTCTTCG GGATAGGGCC GCGCGAGGCC ACCGTGATGG ACCCCCAGCA 59761 GCGCCAGCTG CTGGAGGCGT CCTGGGAAGC CCTGGAGCAG GCCGGGCTGG ACCCCCGGGC 59821 GCTCCGCGGC AGCCAGGGGG GTGTGTTCGT CGGCGCGGCG AACCAGGGCT ACGTACCGGG 59881 TGACGCGGCG GCGTCGGGAC GTCTGCCGGA GGGTTCCGAC GGCTATCTGC TCACCGGCAA 59941 CGCCGACGCC GTCCTGTCGG GCCGGATCAG CTACTTCCTG GGCCTGGAAG GCCCGTCCAT 60001 GACCGTCGAG ACGGCCTGCT CCTCCTCCCT GGTGGCACTG CACCTGGCGG TGCAGGCGCT 60061 GCGCCGTGAG GAGTGCGAGT TCGCCCTGGC CGGAGGGGTC GCCGTGCTCG CCAACCCGGC 60121 CGCCTACGTG GAGTTCGCCC GGCAGCGGGG ACTCGCCCCG GACGGGCGCT GCAAGGCGTT 60181 CGACGACGCG GCGGACGGTA CGGGCTGGGC CGAGGGCGTC GGCGTCCTGG TGGTGGAGCG 60241 GCTGTCGGAC GCGGTACGCA AGGGGCACCG GGTCCTCGCC GTCGTGCGGG GCACGGCGGT 60301 GAACCAGGAC GGTGCCAGCA GCGGTCTGTC CGTGCCCAAC GGGCCCTCCC AGCAGCGGGT 60361 CATCCGCCGA GCGCTGGCCG ACGCCCGGCT GGAGGCCGGC CAGATCGACG CGGTGGAGGC 60421 CCACGGCACC GGCACTCGGC TGGGGGACCC CATCGAGGCG CAAGCCCTGC TGGACACGTA 60481 CGGAGAGGAG CGGAGCCCCG AACGCCCTCT GTGGGTCGGG TCGTTGAAGT CGAACTTCGG 60541 TCACGCACAG GCGGCAGCCG GAGTCGGCGG CGTCATCAAG ACGGTGATGG CGCTCCGGCA 60601 CGGCCTGCTT CCCCGCACGC TCCATGTGAC CAGCCCGACG CGGCACGTCG ACTGGGGCGA 60661 CGGACAGGTG CGGCTGCTGA CCGAGCCGGT CGACTGGCCG CGGACCGGCG CCCCCCGGCG 60721 GGCCGCGGTC TCGGCGTTCG GCGTGAGCGG CACCAACGGG CACATCATCC TCGAGGAGGC 60781 GCCGCCGCCC ACCCGGCCCG AAGCGGTCCG GCAGGCCGGG GAGCGGCGGC CGGTCCTGGT 60841 CCCGTGGACG CTGTCCGGCC GTACGAGGCC GGCGCTGTGC CGGCAGGCCG CGCGCCTGGC 60901 GGCGCACCTC GAACAGCACC CGGACCTCGA CCCGCTGGAC GTCGGGTTCT CGCTCGCCAC 60961 GACGCGCACC CACTTCGAGC ACCGGGCCGT GCTGCTCGCG GACGCCGCCA CCGAGGGCGG 61021 CTCCCGTGCC GACGCGCTCG GGGCGTTGCG GGCGATCGCG GAGGACCGCG ACCCGGGCGG 61081 GGCGGTACGG GACACCGCGC GGGGCGAAGG GCGTATCGCC TTCCTGTTCT GCGGGCAGGG 61141 CAGCCAGCGG CCCGGCATGG CGGAGCAGCT GTACGCGCAG TACCCGGCGT TCGCGCGGGA 61201 ACTGGACACG ATCGCGACGC ATCTGGACGC CCATCTGGAC CGTCCGTTGG CGACGGTGAT 61261 GTTCGCGCCG GCCGGTACGG CGGAGGCCGC GCTGCTCGAC GGCACGCAGT ACGCCCAGGC 61321 GGCCCTGTTC GCCGTAGAGG TCGCGTTGTT CCGGCTCTTC GAGGGCTGGG GGCTGCGCCC 61381 CGACGTACTG CTGGGCCATT CCGTGGGCGA GCTGGCCGCC GCCCACGTGG CCGGGGTGTT 61441 CGGGCCGGCG GACGCCTGCT CGCTGGTCGC CGCACGCGGC CGGCTCATGC AGGAGCTGCC 61501 GGCCGGCGGC GCGATGCTCT CGGTCCGTGC CGCCGAGCAC GAGGTGCGGG AGCTGATCGC 61561 CGGGCAGGAG GACCGCATCG CGGTGGCGGC CGTCAACGGG CCCCGCTCCG TGGTCGTATC 61621 CGGGGACGAG GACGCGGTCT CGGCGCTCGC CGAGGAGCTG ACCGAATACG GCGTGCGCAC 61681 CAAGCGCCTC AACGTCAGCC ACGCCTTCCA CTCCCCACGT CTGGACTCCA TGCTGGAGAC 61741 GTTCCGCCGG GTCGCGGAGA CGGTGGAGTA CCGCGAGCCG ACGCTCGACG TGATCAGCGG 61801 CCTGACCGGC CGCCCGGCCG ACGCCGGGGA ACTCGCCACC GCCGACTACT GGGTCCGGCA 61861 GGCGAGGGAG ACCGTCCGGT TCCACGACGG GGTGCGCGCC GCGCACGCGC GCGGCGTCAG 61921 CACCTTCGTG GAGCTGGGGC CGGACGGCGT GCTGTGCGGC CTGGCCCTGG AGACCCTGGC 61981 GGAGGAGACC GACGGGGAAG CGGCCGCCGA GACGCCCGGC CGGGCGCGGG CGGCGCTGGT 62041 GCCCGTGATG CGTCGGGAGC GGCCGGAGGG CAGTACCCTC CTGACGGCGC TCGCCACGGC 62101 CCACGCGCGC GGGGCGGAGG TGGACTGGTC CCGGTTCTAC GCCGACACCG GCGCCCGCCA 62161 CACCACACTG CCCACCTATG CCTTCCAGCG CCAGCGGTTC TGGCTGGAGA CGGCGGCCCC 62221 CGCCGCGCCC GCGGCGGGCC AGGGGGCCGG ACCGGCCGAC CCGCAGGACA GCACCGGTCC 62281 GGCCGCCCGG CCCACGCTGA CGGAACAGGA CCTCCTCCTG CTCGTGCGGA CGGAAGCGGC 62341 GGCCGCACTC GGCCACGCCG AACTGGAGGA CGTACCGGCC GACAGCCTCT TCGGCGACAT 62401 CGGCTTCGAC TCGCTCGCGG CCATCGAACT GGGCGCCGCC CTGACCGGCG CCACCGGGCT 62461 GGAAGTGCCG TCGTCCCTCG TCCTCGACCA CCCCACGCCC AGGGAGCTGG CCGCGCACCT 62521 GGCAGCCGCC CGGACGGCCG CCGACAGCGA CGACACGTCC CCCGAAGGCC CGGACACGGC 62581 CGGTGAGAGC AGCCTGTCGG CGATGTACCG GCGGGCCGTG CGGCTCGGCC GGGCCGAGCC 62641 GTTCATCGGC ACACTCGCCG AACTCGCCGC CTTCCGGCCC GTCTTCCCCG CCGATCACAC 62701 CCTCGCGGAC GGCGAGACCG TCGGACAGGC GGCCGCCGCC TGGCAGCCGG CTCCGGTGCG 62761 CCTGGCCACC ACGGACGGTG AGGGACCGGA GCTGATCTGC TGCGCGGGTA CGGCGGTGGC 62821 GTCGGGACCG GAGGAGTTCA CCGCGCTGGC CGCGGCCCTG GGCGACCGGC TGACCGTGTC 62881 GGCACTGCGC CAGCCCGGCT TCCGCGCGAA CGAGTTGCTG CCCGGCTCCC TGGACGGGCT 62941 GCTCGACGCG CAGGCGGACG CGGTGCTGCG GCACACGGGT GACAGGCCCT ACGCCCTCCT 63001 CGGCCACTCG GCGGGCGGGG CGCTGGCGCA CGCGCTGGCC TGCCGACTGG AGGAGCTCGG 63061 CGCGGGTCCC GCGGCGCTGG TCCTGGCCGA CGTCTATCTG CCCAGCTCGC CGGGGGCGAT 63121 GGGGGTGTGG CGCAACGAGA TGCTCGACTG GGTCATGCGG CGTTCCGTGG TGTCCATCGA 63181 CGATGCCCGG TTGACGGCCA TGGGCGCCTA CAACCAGATG CTCCTGGAGT GGACACCGCG 63241 GCCCACGAAG GCGCCGGTCC TGTTCCTGCG CGCGACGGAG CCGGTGAGGC CGTGGTCCGG 63301 AGAACCGGAG AGCTGGCGGG CGCACTGGGA CGGCGGCGAC CACACCGCCG TCGACGTGCC 63361 CGGCACCCAC CTGACGCTGA TGACCGAGCA CGCCCGCCAC CTCGCGGCGA CCCTCCACAC 63421 CTGGCTCGGC ACCCTGTGAA CCACGCCCGG GGCGGCTTCG CCGCGCGTAG GACTGCCGCC 63481 TCCCCCGACT TCCGTACACC GCGACACCTT GGAGGACTCC CGTGACAACG CAGTGGACCA 63541 CCCCGTCCGT GCTCGGCCGC AGACTGCAAC GCACCTACGT GGGGCACTGG TTCGCAGGAA 63601 CGCAGGGAGA CCCCTACGCG CTGATCCTGC GCGCCCAGCG GGACGACACC ACCCCCTACG 63661 AGGAGGACGT CCGCGCACGC GGACCGGTGT TCCACAGCGA GGTGCTCGAC ACCTGGGTGA 63721 TCACGGACGG CGCTCTCGCC CGGTCCGTCC TGACCGACGC CCGCTTCGGC GGGCTGACGC 63781 GCGCGGGAGG ACGGTATCGC GCGGAGCTTC TCCCTCCGGC GGGCCCCGAG GTCGGTCCGG 63841 CCCGCGCAGG GGTACGCGGC GGCGTGCGGG CCGACGCCGA TCCGGCGGTG TCGGCGCAGG 63901 ACGAGGTGGT GGTGGAGGCC CTCGCCGAGC AGCTCTCACG CACCCTCCTG GGCGGACTCG 63961 GCGACGACTT CGACCTCGTC GCCGCCTTTG CGCGACGCCT GCCGGCACAG GTCCTGGCGG 64021 AATTCCTCGG GCTGCCCGCA GCCGCGCGCA GCCGGTTCGA GGAACTGCTG GCCGGCTGCG 64081 CCCACAGCCT CGACAGCCGG CTCTGTCCGC AGACGCTCGA CATCACACGG ACCGGCCTCG 64141 GAGCGGCGGC CGAGCTCCGG GAACTGCTCG CGCGCCACCT CGGCGGGAGC GGACCACGCT 64201 CCGCTCAAGC GGCAGTCTCC CTGGCAGTCG AGGTGGCCGC ACCCGCCGGC GCGCTCATCT 64261 GCAACGCGGT CGAGGCGCTG AGCAGCTCTC CCGGGCAGTG GAACGCCCTC CGCCAGAACC 64321 CGGAGAAGGC CGACGCCGTC GTGGCGGAGA CCTGGTGGCG ACGACCGCCG GTGCGGGTGG 64381 AGAGCCGGAT CGCCCAGGAG GACGTCGACG TGGCCGGAGT GCCCGTCCCC GCGGACGGGC 64441 ACGTGGCGAT CCTCGTCGCC GCCGCCCAGC GCGACCCGGC GATCACCCCG GCCCCGACGA 64501 AGGACGACAC CGGCACCCCC GGACAGGGCG ACTGCGGCGT GCCCCTGGGG CTCGTCGGCG 64561 ACGCGCACGC CACCTCCGCC GCCCGGACGG TCCGCGCCCT CTGCCGCGGT GCGCTGCGAG 64621 CGCTCGCGCA GGAGGCACCG GGCCTGCGGC CGAACGGGAC CCCGGTGCGC CTCAGGCGGG 64681 CACCCGTCAC GCTCGGCCAC GCCCGCTTCC CCGTCGCCCG GACGGGCCGG GGGACACCGA 64741 CCGACGCGGG CGCGGCATGA GCACCCGCGA CGACCACCGA CTGCCGAACG GGGAGACGAG 64801 CCGATGCGCG TCCTGATGAC GTCGATCGCC CACAACACGC ACTACTACCA CCTGGTGCCG 64861 CTCGCCTGGG CCCTGAAGGC CGCGGGCCAC GAGGTGCGCG TCGCCGGCCA GCCCCGCGTC 64921 ACGGACATCA TCACCGGGTC CGGACTGACC GCCGTGCCGG TCGGTGACGA CGAGGACATG 64981 ATGGAGCTGT TCGCCGAGAT CGGCGGAGAC ATCACCCCCT ATCAGGAGGG ACTGGACTTC 65041 GCCGAGGAGC GGCCCGAGGC ACGGTCCTGG GAACATCTGC TCGGACAGCA GACCGTTCTG 65101 ACCTCGCTGT GCTTCGCACC GCTCAACGGC GACTCGACGA TGGACGACAT CGTCGCGCTG 65161 GCCCGCTCCT GGCAGCCGGA CCTGGTGATC TGGGAACCCT TCACCTTCGC CGGAGCGGTC 65221 GCCGCCCACG CCGTGGGCGC GGCGCACGCC CGCGTCCTGT GGGGTCCCGA TGTCATCGGC 65281 CGGGCCCGGG AACGGTTCGT GGAGGCCAAG GCACAGCAGG CTCCCGAACA CCGGGAGGAC 65341 CCGATGGCCG AGTGGCTCGG CTGGACCCTG GAGAGGCTGG GCCTCCCGGC CGCCGGAGAC 65401 GGGATGGAGG AGTTGCTGAA CGGCCAGTGG GTCATCGACC CGGGCCCGGA GAGCGTCCGG 65461 CTCGACCTTC GCGAGCCGAT CCTGCCCATG CGTTTCGTTC CCTACAACGG ACCTGCCGTC 65521 GTCCCCGGAT GGCTGTCCGA GAAGCCGAAG CGACCGCGCG TCTGCCTCAC CCAGGGAGTG 65581 TCGGGACGCG AGACCCACGG CAAGGACGCC GTCCGCTTCC AGGACCTGCT CGCGGCGCTC 65641 GGCGACCTCG ACATCGAGAT CGTCGCCACC CTGGACAGCA CCCAGCGGGA GAACCTGACG 65701 GAGGTCCCCG ACAACGTCCG GATCGTCGAC TTCGTCTCGA TGGACGTGCT GCTGCCGAGT 65761 TGCGCCATGA TCATCTACCA CGGTGGCGCC GGCACCTCGG CGACGGCCCT CCTGCACGGC 65821 GTTCCGCAGG TCGTCATCGG AGCGCACTGG GACGTGCCGG TCAGGGCACG GCAGCTCGAC 65881 GACCTGGGCG CCGGCATCTT CATCCGGCCC GAGGACCTCG ACGCCGCCAC ACTGCGCGCG 65941 GCGGTTCAGC GCGTGCTCAC CGAGCCCTCC CTCCAGCGGG CCGCGGACCG GCTGCGGGCC 66001 GAGATGCGCT CCAACCCCAC GCCGGCCGAG ACCGTCACGG TGCTGGAGCG GCTCTCCCGG 66061 AGCCACCGAC AGCCCCGCTG ACCACACGCG GTACACGGTG CGGGCCCACG TGCCGGGGGC 66121 TCCACCGTCG CCGGCGGTCG TCGGATCGCC GTCCGGCCAT GTCCCGGCAC CCAAGGACGG 66181 AGCAGAGCAG AACATGGAAT TCGAAGGTCA GGTCGCGCTC GTCACCGGGG CCGGCAGGGG 66241 GATCGGCCGT GCGACGGTCG TCCGCCTCGC GGAGGCCGGA TGTGACATCG CCCTCCACTA 66301 CAACCAAGCG AAAGCGCAGG CCGAGGAAGT CGCCGAGCGC ATCGCCGCAC TGGGCCGCAC 66361 GGTCGAACTG TTCCCGGGCG ACCTCTCCCG CCCCGAGACC GGGCGACAGC TCGTGGCCGC 66421 GGTGCAGCAG AAGTTCGACC GGATCGACAT CCTGGTGAAC AGCGCGGGCA TCACACGGGA 66481 CAAACTCCTG CTGTCCATGG AGGCGGACGA CATCCACCAG GTCATCGCCA CCAACCTCGT 66541 CGGCCCGATG TTCCTCACCC AGGCGGTCGC GCTCACCATG CTGCGTCAAC GCTCCGGGCG 66601 CATCGTCAAC ATCTCCTCCG CCGCCGCGAG CAGGCCCGGA AAGGGCCAGT CCAACTACGC 66661 CGCGTCCAAG GCCGGTCTGG AGGCCTTCAC CAGGGCCATG GCGGTGGAAC TCGGATCCCG 66721 CGGAATTCTC GTCAACGCGG TCGCTCCCGG CATCGTCAAG ACCGGCCTGA CCGAGGCTCT 66781 CCGCGAGGGG GCGGAGCCCG AACTCCTGGC CCGGCAGGTG ATCGGTTCCT TCGCCGAACC 66841 CGAGGCGGTG GCGGAGGCGG TGGCCTACTT GGCGAGCCCG CGCAACACGC ACACGACGGG 66901 CACGGTCCTC ACCGTCGACG GCGGGCTCAA GATGGTGTGA GGCCCACCGG GCATCGGACA 66961 GCCGGTGGAT CCGCCGGAGG CGGAGACCCG CGCACCGCGG GCGTCGACCC GCGCACCGCG 67021 GGCGCGCGTG GGGGCGCCCG CGGTGCGCGA AGGCCGCCTC TGGCTCGCGT CACCGGAAGA 67081 AGCCCGATTC CCCAGCGGGC GACCGTAGCC GGAGCGTTGG ACCGCCCTGC TCCGCACGTC 67141 GAGCCCCACC GTGGTAGCGG CGGACATGCC CAGGGGGCGC ACGCCCGGAT CCTGCCGCAC 67201 GACCAGGCGC ACCAGGGTTT CGGCGAACAC GGCGGCCGAC GCCGCGGGGT TGCCGCCGCG 67261 GCACGGCCGA CGCGCGCTGG TCGCACGGGG TGAGCCCGCG GGAGCGGAGG GCGCCGGTTC 67321 GCTCAGGACG CCGGGATCTC CGCCGGGACG ACGGACTCGG GGGCGCCGTC GGGGCCGGGC 67381 CTCGTGCCAC CGTCGGCGTC GAGCTGCGGC GGATCGGAGA GCTGCTCGCG CACGTACCCC 67441 CACACCACGG CGACGAGGGC GGCGACGGGC ACGGCGAGGA GGCTGCCGAC GATGCCCGCC 67501 AGACTGCCGC CCAGGGTGAC GGCGAGCAGG ACGACGGCGG CGTGCAGTCC GAGTCCGCGG 67561 CTCTGGATCA TGGGCTGGAA GACGTTCCCC TCCAGCTGCT GCACCACCAC GATGATCGCG 67621 AGCACGATCA GGGCGTCGGT CAGGCCGTTG GAGACCAGGG CGATGAGCAC GGCGACGAAT 67681 CCTGCTAACA GCGCGCCGAT GATCGGCACG AAGGCGCTGA CGAAGGTGAG TACGGCGAGC 67741 GGCAGGACGA GCGGGACGCC GAGGATCCAC AGGCCGATGC CGATGAGGAC GGCGTCGAGG 67801 AGGCCCACCG CGGCCTGGGA GCGGACGAAG GCGCCGAGGG TGTCCCAGCC GCGTTCGGCG 67861 ATCGTGGTGG CGTCGGTCGC GAGGCGGCCG GGGAGCTGAC GGGCGAGCCA GGGCAGGAAG 67921 CGCGGCCCGT CCTTGAGGAA GAAGAACATC AGGAAGAGCG CGAGGACGGC CGTGACGACC 67981 CCGTTCACCA CCGTGCCGAC GCCGGTGGCG AGGGTGGTCA GCAGGGATCC GACGCTGTTC 68041 TGGAGACGGT CGGTCGCGGT GTCCAGGGCG CCGGTGATCT GGTCGTCGCC GATGTTCAGG 68101 GGCGGACCCG CGGTCCACTC GCGGAGACGC TGGATGCCCT CGACGACACC GTCGGCCAGT 68161 TCGCCGGACT GCGAGGCGAC GGGCACGGCG ATGAGCGCGA CGGTGCCGGC GGTGACGGCG 68221 AGGAAGAGGA CGGTGACCAC CGAGGCGGCG AGCGCCGGCG GCCAGCCGAG ACGGCGCAAC 68281 AAGCGGGCGA AGGGCCAGGT CAGCGTGGTG ATCAGCAGAC CGATGACGAG TGGCCACACG 68341 ATCGACCACA TCCGGCCGAG CAGCCAGATC ACCGCCGCCG TGCCCAAGAG CACCAGCAGA 68401 AGCTCCGTCG ATATGCGGGC CGAGGCCCGT AGCGCGGCAC GTGTTCTCGC AGGACTGAGA 68461 GAGGCAGACA TGGCGATCAC CCTAGAGCGG CCCGGGCGGC CCGCTGCCCC CGTGCCCCGA 68521 TCCTTCGCGC CGGGGTGACG CGCATCGGGG GTTCCGGCAC TGCCTGAGCG CCTGCACGGA 68581 CGGGGCGGGT TACGCCGAGG GGAAGCAGCC GGCTCCGGAT CGACAGGAGT GCGGGTGACG 68641 GTCGTACACC GGCGCTACGT CGCCCACTCC GCGGCGCACA AGGGCGGTCG CCGTCTGGCC 68701 CCTCCCCGCG TCCGACGACC GCCCACCCCT CGTCAGGGAG CGGGGTCCGG GGCGAGGTGG 68761 ATACGGGCCG CTACCGGGAG GTGGTCGCTG GCCGTCGCGG GAAGGGTCCA TGCCGAGGCG 68821 GCCCGGACGC CCCCGAGAAG GATCTGGTCG ATCCGGACGA CCGGCAGGCG CGCCGGCCAG 68881 GTGAAGCCGA AGCCCGCGCC CGCCGCGGCC TGTGCGGAGA CGAGACGGTC GGTGAGGGGG 68941 CGCAGTGCGC GGTCGTCCGT GGAGCCGTTG AGGTCGCCCA GGAGGACGAC GCGCCGGACG 69001 GGCTCGGCCC GCACCTCCGC CGCCAGCAGC CCCAGCGCCT CGTCGCGCGC CCCGGCGGTG 69061 AATCCGCCCG GGCCCACGCG GACGGACGGC AGATGGGCGA CATAGACGGC CAGCGGCCCG 69121 CCGGGCGCGT CCACCGTGGC CCGCATCGCC CGCGTCCACG GCATGATCGG CACAGCCCGC 69181 GCGTCGCTCA GCGGATGCAC GCTCCACAAG CCCACCGTGC CCTCGTAGAA GTGGTACGGG 69241 TACGACTCCG CAAGGGCCCG CTCGTAGGCG GGCGCCGTGG CCGGGCTCAG CTCCTCCAAC 69301 GCCAGTACGT CCGCCCCGGC GGCGAGCAGG CTCCGCACCG TTCCGGCGGG GTCGGGGTTG 69361 GCCTGCTCGA CGTTGTGACT GACCAGCGTG AGGTCCCCAC CGGGCGTCGT CTTGTCGGTC 69421 AGCGCTCCGC CGAAGGCCGT CAGCCAGGCC ACGGCCGGCA CCACCAGGGC CACCACCGCC 69481 GCCACCCGCG CGCGCCACAG CAGGGCCGCG GTCACCAGCA CGGGCACGGC CAGCGCGCTC 69541 CAGGGCAGCA AGGTCTCTGC CAGACTGCTC AGCCGTCCGG GCAGTCCGGG GAGCCGCCCA 69601 TGGCCCGCGA CGCTCACCGC GAGGAAGACG GAACAGCCCG TGACCGCCGC CCCGCGGCGT 69661 CGCCACCACC GCCGGCGCGG ACCGGCGTCC CCCACGCCGA CCGCGGCTCC GGGAGCGCGG 69722 CCCCTGCCGT CCGCCGTGCC GTCCGCAGCC AGGGAGCAGA CGGTCTGTTC CGCCCTGCCG 69781 TCCGCCGCAG TGGAGGGGGC GCTCTCCGCT GCCCCGCTGT CCGGCGCCGC CCGGGAGGGG 69841 ACAGTCTGTG CCGCCCTGCC GTCCGGCGCC GCGAGGAAGA CGGAACAGCC CGTGACCGCC 69901 GCCCCGCGGC GTCGCCACCA CCGCCGGCGC GGACCGGCGT CCCCCACGCC GACCGCGGCT 69961 CCGGGAGCGC GGCCCCTGCC GTCCGCCGTG CCGTCCGCAG CCAGGGAGCA GACGGTCTGT 70021 TCCGCCCTGC CGTCCGCCGC AGTGGAGGGG GCGCTCTCCG CTGCCCCGCT GTCCGGCGCC 70081 GCGGGGGAGG GGACAGTCTG TGCCGCCCTG CCGTCCGGCG CCGCGGGGGA GGGGACGGGC 70141 TCCGCCGTCC CGCCGTCCGG CACCGCGGCC GGATCCCGGC GTGTCGTCGC CGTCATCGTT 70201 CCCCGCCCTG GGTTCCGGCG GCGGCCAGCC GCTCGCGGAC GGCGGTGAGC AGGCCACGGG 70261 CCGCCTCGAC CGCGGCCCGG AGCCCCTCGG CGGGCGTCGT GTTCGCCCGC TGGTGCAGGA 70321 CGGCGCCCAC CAGCAGCCGG GGCGCGCCGC CCACGCGCAC CTCGTAGGCC CACAGGAGGT 70381 TCCCGCCCGC CGGGGTGCTG GAGCCCGTCT TCACACCGAG GACGCCCGGG GTGTCCAGCA 70441 GGGGATTGGT GTTGGTGATC GTCCCGAGGC CCGGGACGGT GGTCTCGCGG GTGGCGACGA 70501 CCGCCCGGAA GACAGGGTCC TCCATCGCGG CCCGCGTCAG CCGCACCTGG TCGGCCGCGG 70561 TGCTTGTGGT CGTCGGCTCG ATGCCGCTCG CCCCCGTGTA GACCGTGTCC TTCATCCCGA 70621 GCCGTACGGC GGCGCGCCGC ATCTTCGTCA CGAAGGCCGC CTGGCTGCCG GAGTCCCAGC 70681 GGGCCAGCAG ACGGGCGACG TTGTTGCCGG AGGGGATGAG GAGCAGTTCC AGGAGCCGGC 70741 GCTGGGAGTG GCGTTCGCCG GACCGTACCG GGACGGTCGA CTCGCCGCCG ACCCCCGCCT 70801 CGTGCGCGGC CGTCCGGTCC ACTTCGATCA GGGGGCCGTC CTCGTCGGGC CTCAGCGGAT 70861 GCTCTTCGAG GATGACGTAG GCGGTCATCA CCTTCGTCAG GCTCGCGATC GGTACGGGCC 70921 GCCGCTCGCC CCGCTCGCCC AGCGAGCCGG TTCCTTCGAG CTCGACGGCG CTCTGGCCGT 70981 CCTGCGGCCA GGGGAGCGGC CCGATGTCGG AGACCGGTAG TCGCTCGCCT CCCGCCGCCG 71041 GAGGCGCGCC GGAGGGCGAG GCGACGGTGA TGCCCAGGGC CGTCAGCAGG GCCACGGACA 71101 GGGCACCGCC GACGAGGCGG TGACGGGGGG TGCGGGGCAG GGACACGGGC CGCCTCCAGG 71161 GGCTGCGGTA CGGGATCGGT ACGGCAGCAA GACTCCGGGG GCTACGTCTC CGCCTCACGG 71221 TCGGGAGAGC GCGGCCCGCG CTCGGGAACC CATCGGTCGT GTATCGGCGG GGCGGCGGCG 71281 ACCGGCCGCC GGGCGACGCG GAGGGAGCGC CTGAGGGGCG GGGCGTACCG ACAGGCGACC 71341 GTCTGGGGTG GGGAGGCCCG CGGGCTGTCC CGGGGACCGG TTCACGCCTC GGACGTCTGC 71401 CCGTCCTCGG GCAGGCTCAG GGTCGCGACC GCTCCTCCGT CCCGGGCGTT GGCGAAGGCC 71461 AGGGTCGCGC CGATCACCCT CGCCTGGCCG GACGCGATCG TCAGGCCAAG GCCGTGCCCG 71521 TGCCCCCGTT CGGCCGAGCC CGTGCGGAAC CGCTGGGGGC CGTGGGACAG CAGGTCGGCG 71581 GGGAAGCCGG GGCCGTGGTC CCGGACGGTC ACGGTCCGGC CGGCGACCGT GACCTCCACC 71641 CGACCCGCGC CGTGCCGGTG GGCGTTGACG ACGAGGTTGG AGACGATGCG GTCCAGGCGC 71701 CGGGGGTCCG ACTCGACCAC TGCCGCCCCC TGTCGCGTCA CCTGCGCCGC GAGGCCCGTC 71761 CGCGCCACCG AGTCCCGGAC GAGGGCGCCC AGGTCGACCG GTCCCTGCTG GGCCGTCTCG 71821 GCGCCCGCGT CGAGCCGGGA GACCTCCAGG AGGTCCTCCA CCAGGTCGCG CAGCACCCGT 71881 ACCCGGCTCT GGACCATGTC CGTCACCTCG CCCTCGGGCA GCAGTTCCGC CGAGGTGACC 71941 AGGCCCATCA GCGGGGTGCG CAGCTCGTGT GCGACGTCGG CGGTGAAGCG CTGCTCGGTG 72001 TCGATCCGCT GCTGGAGGCT GTCGGCCATC GAGTCGACCA CGGCCGAGAT CTCGGCGACC 72061 TCGTCGCCTC CGCGGACCGT TCCCGTCCGG GCGTCGAGGT CGCCCGCCGT GATGCGCCGG 72121 GCCGTGCGGG CGACCCGGCG CAGCCGCCGG GCGGGGAGTT CCGTCGCCAG GGCCGTGGCG 72181 GGGACGACGA CGCCCAGGGT GAGCAGCGAG TACTTCCACA TGTGACGGTC CAGGGCCTGC 72241 CGGGTCAGCA GGTCGGCGGT CATGTCGACC TCGACCGCGT ACAGCTTCCC GCCCTCCCGG 72301 CGGGCCGCCC GGAAGACGGG GGCCGGGGGC CCGTCCTCGT AGAGGGTGGC CTCGCCGCCG 72361 TGCTCGATCT GCCTCAGCAG GGCCTCGGGC AGTTCCTCGG GGGACACCCG GGGCCCTTCC 72421 TCACCTGCTG CGTCGGCGTC CTCCAAGGCC GTTGCCAGCG CCACGTGGGC CCTGCCCGCG 72481 CCCTCGTGCA GGGAGCGCCG CAGCACCGAG TCGTGCACCA GCACTCCGAC GGTCAGCGCC 72541 ATCGAGGCAC AGGCGAGCGC CACCAGGAGG ACGATCTTCC AGCGCAGCGA GCGGGAGCGC 72601 GGTACCAGGC CCGTGACGGC TCCCCGGGGG GCCCGGCTCA CCGCTTCCAC TTGTAGCCGA 72661 AGCCCCGGAC CGTCTCGACG CGCTCGGCGC CGATCTTCTT GCGCAGCCGC TGCACGCACA 72721 GGTCGACGAC CCGGGTGTCC CCGTCCCAGC CGTAGTCCCA CACCTCGCGC AGGAGGGTCT 72781 GACGGTCCAG CACGATCCCG GGGTGCGCGG CGAACTGGAG CAGCAGCCGC AGCTCGGTCG 72841 GGGCGAGCGC GATCCGCTCG CCGCCCCGGC GGACCTCCAG GGCCGCGGGG TCGAGGGAGA 72901 GGTCGCCGAA GAGCAGCGGG CCGGCCGGCG TCGCGGGGTC GGCGGGTCCG GGGGCGGGGG 72961 ACACGAAGGC GGCCCGGCGC AGCAGCGAAC GGATGCGCGC CACCAGGACG GCGGTGTCGA 73021 CGGGCTTCAC CACGTAGTCG TCGGCCCCGG CCTCCAGGCC GGACACCACG TCGAGGGCGT 73081 CACCGCGCGC CGACATCATC AGGATCGGGT CCGTGGCCGT CTCCCGGATG CGCCGGCACA 73141 GTCCGATGCC GTCCAGGCCC GGCAGCATCA CGTCGAGCAG CACCAGGTCG TGCCGTCCCT 73201 CCCGGAAGAG TTCGAGCCCG GTCAGTCCGT CGGCCGCGAC GCGCACGGGG TAGCCGTAGC 73261 GCTCCAGGGA CATCGCGACG GACCGCCGGA TCACCTCGTC GTCCTCGACC AGCAGGACGG 73321 TCACGGTCGC AGGCGCGGGC GCCGACACGG AATCAGACAT GTCCATCTCT CGGGCACGGG 73381 GCGGGGCGGG CCGACGCGCG GCCCGGCCCT CCATCATGCC TCACTCGCGC GCCTCCCCCG 73441 GCGCCGCCGG AGAGCCGTCG GCACGCCTCT GAGCTGGTCT GATACCTGAC TGATACATCA 73501 TGGCGCGGTG ACCGACACAC GCCCGAGCGG GGACGGACAC GGAGGCGGCG CGCCGGACAC 73561 AAGATGCCGC GGGAGCCGAT CCGGCGCCCA CCGAGGCCGT GTGAACGACG CCGTCCGGAA 73621 CCGCACGCCC GCGGGGGCTC GTGGCGGGTG TCAGTGGTGT GCGGCAGGCG CGGGCAGCGT 73681 CTCCGGAGCG GGGTCGGTCC TGCGGCCGAG GTGGTTGAAG GCGAGGTTGA GGAGGACGGC 73741 GACCACACAT CCGGTGCTGA TGCCTGAGTC GAGGACGATG CGGGCGCCTT CGGGGAAGGC 73801 GTGGTAGAAG TCCGGGGCGG CGATGGGGAT GATGCCGGCG CCCAGGGAGA TGGCGACGAT 73861 GAGGACGTTG TCGCCGCGTT CGAGGGCGGC TCCGGCGAGG GTCTGGATGC CGCTGGCGGC 73921 GACGGTGCCG AAGAGGGCGA TGCCCACTCC GCCGAGGACG GGCTGGGGGA TGAGCGCGAC 73981 GACGGAGGCG AGCAGCGGGC AGAGGCCGAG CAGGAGGAGG ATGCCGCCGG CCGCGGCTAC 74041 GACGAAGCGG CTGCGGACCT TGGTGATCGC GACGAGGCCG ACGTTCTGGG CGAAGGCGCT 74101 GGCGGCGAAG CCGTTGAAGA GCGGGCTGAG GGCGGTGCCG AGGCCGTCGG CGCGGAGCGC 74161 GGCGGCCAGG GTCTTCTCGT CGGCCGGCCG CTCGACGATC TCACCGAGGG CGAGGACGTC 74221 GGCGGTGGAC TCGGTCATCG ACACGAGCAT CACGATGCAC ATGGAGATGA TCGCCGCGGC 74281 CGCGAACTGC GGAGCGCCGA AGTGGAACGG GGTGGGGAGT CCGATGACGT CGGCGTCGCC 74341 TACGGCGCTG AAGTCGGCGA CGCCCAGCGG CAGCGAGAGG AGCGTGCCGG CGACGAGGCC 74401 CAGCAGGATG GAGATCTGCT TGAGGAAGCC CGTCAGGACG CGGCGCAGGA CCACGGTGAT 74461 CAGCAGGGTG GCGGTGGCGA GGCCGATGTA CGTGAGGCTG CCGTAGTCCG GTGCCTGCGC 74521 GTTGCCGCCC TGGGCCCAGT TGAACGCGAC GGGCAGCAGG GAGACACCGA TGAGGGTGAT 74581 GACCGTGCCC GTGACCACGG GCGGGAAGAA GCGGATCAGT TTGCAGAAGA AGGGGGCGAG 74641 GAGGAATCCG AAGACGCCGG CGACGATCAC GGCGCCGTAG ATGACGGGCA GCGCGTCGTC 74701 GGGGCCTTCG GCCTTCGCTA TCGCGAGCAT CGGTGCGACG CCGGCGAAGG AGACGCCGTT 74761 GACGAACGGG AGCCGTGCTC CGACCTTCCA GAAGCCGAGC GTCTGCAGGA GCGTGGCGAT 74821 GCCCGAGGTG AACAGGCTGG CGCTCATGAG GAACGCGATG TCCGCGGTGG ACAGGCCGAC 74881 GCCGATGCCG ACGACCAGCG GCGGCGCGAC GACGCCGGCG TACATGGCGG CGACGTGCTG 74941 CAGACCGGCG CTGAAGAGCT TCAGCGGGGG CAGCATCTGG TCGACCGGAT GGGTGTCGCC 75001 CGGTCTTGCG GGGGTGTCGG GACGAGCGTC GGTTCCGTCC TCGGTCTTCG TCGGTTCCGG 75061 GGCGGGGCGG GATTCCGGCA TGGCGTGTCT CCTGGCCGCG GCGGTCTCGT GGGAGCGCGG 75121 GCAGCCCTGT GGGAGAGCCG GCGTCGCTGA CGCACGGCTC TGCGGATGGG GGTGGTGACG 75181 GGGTGGGGAG GATGCGGCAC CGGGCGTGGG ACGAGAGGCC GTCGTGCCTG GGTGCCGCGG 75241 CCGGAGAGCG GGGAGTGGGG CGCCGGAGAA CGGGCGGGAG GGATTCGTGT CCCGGGGTTC 75301 CCGCGGTCCT CCGGCCGGCC GGCGCGCAGC TGTCCGTGAT GCGCGTCGTG CCACTCCGTC 75361 CGGCGAAGTC GGAACAGTTC CTCACGGGGC GGCGTGGGTG TCAAGAGGCG GGACGGGCCG 75421 GGTTGAGGAC CTCCCGGACG TGGTGCCAGA GGTGCAGGTC GATGTGTTCG AGGAAGTCCG 75481 CCGCCCGGGC CTCCGCGCGG GCCGCCTGAC GGGGCGGGCC GCCGGCCGCG CCCTCCCATT 75541 GCTGGTAGGT GAGGTGGAGG CGTTCGAGGG CGTGGCCGAG TACGGCGGGG TCGAGCGGCA 75601 CGATGCGGGA AAGGGCCCCC ACGTAGGGGG GCCACCAGGT GGTGGCGGCC TCTCTGAGCA 75661 GGACGCGGAG CCGGCCGGTC CTGCCGCACG CGGCGACGAA GCAGGCCGGT GGCGGGCAGA 75721 GGACTCTCAG GAGGGCGTCC GTCTGGGCGG GGGTCCCCTG CCAGCGGTTC CGGCGTTCGG 75781 CGTCCTCCCA CTGGCCGCGG GTGAGGCCGA GCTCGGTCGC GGTCTCGTTG ACGGTGAGTC 75841 CGGCGACGGT ACGGCACTGG GCGAGGGTGC CGGGCTCTTC GACGAGATCG ACCGGAGAGC 75901 ACCAGAGGGC CGCCGCGAGG GCCTTCACCT GGGTGTTGTC GGGGGTGGCG GTGCCGGCTT 75961 CCCACGCCTC GACGAGGCCG GGGTGCGCGG GGTGTCCGCA GTAGGCGGTG ACGGCCCAGG 76021 CGACCTGGCC GAGCGTCAGG CCGAGCTGGG CGCGGACGGC CGCGGCACGG GTGGGATCGA 76081 AGCGGGGCAG GGCATACGGA TCGTCTGCGG GTGGCATAGC GGGACACCGT AGGGACCCCG 76141 CGGTCCACGG CCAAGGGCCG GAACGGTCTC GATGTCGGCT CCGCCGCCCG GCGTTCGGCT 76201 TCTTCGTCGG ATCTCCTGAG CGGGCAGACC GTCGATGACC TGCTCTTTCA TGGGAGGAGG 76261 CGGGCAAGCG GAGAGAAGAG GAGGCTGAGG CGACTGTCGG TTCCTCCAGA ATCCGCGAGG 76321 AACTGGCGCC TTCTCTTGGG GGAGTTGACG AGGTTCAGGC CGGGCCATAA AGTCCCGTCC 76381 CGTCCACAAC GGAAAACTTC TTCCGTCATG CGAAACCTGT GGTGACAGCC GCCCACCCCC 76441 GCGGCTCGCC CCCATCGGCC ATGCTCCCGG TTCGGGCCGT CCCCCGGCAC CGGTCACTCT 76501 GCCCACACGC CCCCGGCAGT CCGCTGCCCG CGGGCGGTGT CTCAAGGACC TGCCTTGCTG 76561 CCCCGCGCCA CTGACCACGC ATCGCCGACC CCACCCCATC CGGTCGACGA GATCCTTCCC 76621 GCCCGCCGCA TGCTGCCCGC CGCCCTCCAA CACGTGGCGA GCATGTACCC CGGCCTGACC 76681 GCACCACCGC TGATCATCAG CAGCGCCCTG GGGCTGACCC CGGCCCAGCT CTCCGCCCTC 76741 CTGGCCGCCG CGCTGCTGAT CGCCGGGCTC GGCACGATCG CCCAGACCCT CGGCGTCTAC 76801 GGCGTCGGCG CCGGGTTGCC CCTCGTCAAC GGCGTCTCGT TCGCCGTCGT GTCACCGGCG 76861 CTCGCCACCG CCGCCACCCA GGGGCGCGAC GGCGCCCTCC CGGCGATCTT CGGGGCCACC 76921 CTCGTGGCGG GACTCCTCTG CCTGCTCCTC GCTCCCGTCT TCTGCCGACT GGTCAGGTTC 76981 TTCCCACCGG TCGTCAGCGG CTGCGTCATC ACCCTGGTCG GCATCTCCCT CCTGCCGGTC 77041 GCCGGCACCT GGGCCCGGGG CGGAGACGCC GAAGCCGCCG GCTTCGGCTC CCCCGCCGAC 77101 CTGGCCCTGG CGGCGACGAC CCTCGTCATC ACCCTGACCG TGCACCGCAT GCTCTCGGGC 77161 CGCTTCCTCG GGCGGGTCGC CATCCTCATC GGCATGCTCG CGGGCACCCT GATCGCGATC 77221 CCGCTGGGCA AGGTCGACCT CGACCCCCTC GCCCAGGCGC CCCTCTTCGC CCTGCCCACG 77281 CCCTTCGGCT TCGGCACCCC GCAGTTCGTC CCCACCGTGA TCGCCACCGC CGCGGTCGTG 77341 ATGATCGTGT CCATGATGGA GTCCACCGCC GCGCTGCTGG CGCTGGGCGC GGTCGCCGAA 77401 CGGCCGGTCC GGGACCGGAC CATCGCCGGA AGCCTCCGCG CCCTCGGCCT CGCCACGGTC 77461 CTCGGCGGCG TCCTCGGCTC GTTCACCAGC ACGTCGTACG CGCAGAACGT CGGCCTGGTC 77521 TCCCTCAGCC GGATCCGCAG CCGCTATGTG GTCACGCTCT GCGGCGCCGT CCTCGTCCTG 77581 ATGGGCTTCG TGCCCGTCCT GGGCTCGTTC GTCGCCCTCG TCCCTCTGCC CGTCCTCGGC 77641 GGTGCGGGGG TGGTCTTCTT CGGCTCCGTC GCCGTCACGG GCATCCGTAC GCTGGCCAAG 77701 GCCGCCCTCG GCACCGGACA CAACGCTGTG ATCGTCTCCG TCACCCTCGC CTTCGGTCTC 77761 TTCCCCGTCC TGGACCCGGA CTTCTACGCC CGTCTTCCCG CCCCGGTGGC GACCGTGCTC 77821 GGCTCGGGGA TCACCGCCGG CTGCCTGGTC GCGGTCCTCC TCAACTACCT CCTGAACCAC 77881 CTGGGCCGCG GCACCGAGGC CGACCCCGAC GCGATCTCCG CGGAACAGGT CACCGCCCTC 77941 GACACCGCGG ACACCGTCCT CGGGCCGAAG CGTTCCTCCG ACTGGACGCC CTTCCAGCCC 78001 TCCGGCAGCC CCTCCGGCAC CCCTGACCAC GGCCGTCACA CCAGGGGCAC GGCACGGCCC 78061 GCTCCCGCCT GGCCCTACGT GACCGGCCCC GTGGACCCCA CCGACACCGG GCGGCACCAC 78121 CGGCCGCACG AGGTTCCGGC GCCGCCCCAC CGACCAGACG AGGTGCCCCC GCCGCTCCAC 78181 CCCTCTGCCG CTCACGAAGG CGAACCCCCG CCCGCCGTCA CCGAGAACGC GGTCTTTCCC 78241 GGACCGCTCC ACCCGCTCCA CCCGCTCCAC CCCCGGCCCA CCGGTCGTCC CGACCGTCCC 78301 CGGCAACGGC ACAGTGCGGA GGCCGACCCC TGGCAGCATC CGCAGACCCC CTCCGCATCC 78361 GGCGACAGCC AGTAGAGACG ACCTCCCCCG ACCTCTTCGC AGAGCCCGGC ATCGCACAGG 78421 CCCGGCGGAG AGGTGGCGCC GACCCACCCG ACCACCGCCG GAAGCGCCCC CGGGGACCCG 78481 TGTCCCACGG ATTCCCCGGC GACAAGACGA GGTAGCCCCG ATGACCACCG TTTCCGCCGC 78541 CCGCCACCGT GCGGGCGGCT CCCCGCGCGG CGGCACGTCC CGCCCGGGCC CCGACGAGAG 78601 AATCGCCCAG GTCGTGGCCG AGGCCCTCGG ATCCGCCCGG ACGGTCCTCG ACCCGGATGC 78661 GCTGCCCGGC CTCGGCACCA CGCGACTCCC GTTCGGCGAC GGGAGGTTCG ACGCGGCGAT 78721 GATGCTCTGC AACGCCCCCG GCGTCCCCGA CGCGCTCTCG CGGCTCGGGG AACTGCGCCG 78781 CGTGACACGG GGCCCCGTCG TGGTCCTCGC GACCGACCCC TCGCGCGTCC GCTCGTTCTG 78841 GCTGGACCGG TACGCCCCCG AGGTCCTGGC CGTCGAAGCG CGGCGTCATC CGCCGATCGC 78901 CGATCTGACC GCCGTCCTCG GGGGTTCCGC CGAGGTGCGG AGCGTCCCCG TTCCCCTCGA 78961 CTGCACCGAC ACCTTCGACG AGGCGTACTA CGGAAGACCC GAGAAGCTCC TGGACCCGTC 79021 GGCCCGCCAG GCGGGGTCGG CCTGGAGCTT CGTGGACGAC CGGGTCCGCG AGGAGTTCGA 79081 CACGACCCTG CGCCGCGAAC TCCGGTCGGG GGAGTGGGAC GAGCGCTTCG GCCACCTCCG 79141 CCGCCGGCCC GTCTACGAGG GATCACTGGT GATCGTCCGT GCCGTCCCCT GACGTCCTCC 79201 CGGGGACGCG CCACCCCCGG GGTCGCGTCA GCGGTCTCCG GCCAGGTGCC CCGAGAGCTC 79261 GCGCATCAGC GTCTCGTGCT GCTGGAGCAG GTAGAAGTGG CCGCCGGGCA GGACCCGTAC 79321 CCGGAAGCCC TCGGGTGCGA CATCCGCCCA GGCGTCCATG TCCCCTACCG CCACGTTCGG 79381 ATCCGTGTCG CCGATCCAGG CGTGCACCGG ACAGCCGACG GCGGTGGGGA CGCGGGGGCC 79441 GTAGGTGCTC ACCACGGTGA AGTCCGCCCG GACCGCGGGC AGCACGAGCT GTCGGATGTC 79501 CGGGTCGTCA AGCAGGGCGG TATCGGTCCC GCCGAGCCCG CGCAGTACGG CGACCAGCTC 79561 GTCGTCCCCC TTCCGGTGCA GGTCGAGCGG GGTCAGCCGG TGCGGGGCCT TGCGGCTGGA 79621 GACGTGGAGG GCGGCGGGCG TGACGCGGTG CCGCTCCTCC AGGCGCAGCG CCACCTCGTA 79681 GGCCAGGGAC GCGCCCATGC TGTGGCCGAA GAGCGTCAGG GGCACGTCCG CGAGCGGCAG 79741 CAGTGCCGCC GTGACCCGGT CGGCGAGCAC GTCCATCCGG TCGACGAACG GCTCGTTGAA 79801 CCGCTCCTGG CGTCCGGGGT ACTGCGCCAC CAGGACCTCG GTGTCGCCGC CGAAGGCGCT 79861 GCCCCAGGCG TGGAAGAAGC TCGCGGAACC GCCCGCGTGC GGCAGGACCG CCAGCCGCCG 79921 CCGGGGCGCG GGAGTGCTGG AGTACCTGCG GAACCACGTC GTGCTGTCCG TGCCGGTCGT 79981 CATGTGTGCG TACACCCCGT CCTCGGGTTC TTGGGGTGCC AGTGTCCCCG CAGGGCCCGG 80041 TGTCCGGACG CGGTGGGGGT CCGGTGGCGA GCCGCTTACG TGTCCCCGCG CTTCCGGGAC 80101 CGGCGGCCGC ACACGTGTCG GCCCCCACGA ACACCAGGGT GCGTGGGGGC CGATGCGTGT 80161 TTCGAGTCCT GGTCTGACGA TTTCAGGCCG AAAGATATGT CGGACTTTAC AGCTGCGATC 80221 GAAGCCGATC GATAATGCCG TGGACGGGTA ACGTCGGAAT CACTCGGTGC TCTTGAGCGC 80281 ACCACTCACG TTGACGACCT CGTGGCACTC CCGCGCCTGC TGTCCCGTCG CGGGCGTACC 80341 GGGCTTCGTG CAGGTCACGT CGATGGTCAC GGTGTCCTTC GCGCCGATCC TGATGGGAGT 80401 CACCCAGTGG TAGTCCTGGT TGCGGAACGT CTCCAGCGCG ATCGTGGTGA TCTTGCGGTC 80461 CCCGAAGGTG ATCGTCATCA CCCCTTCGTC ACCCTGGAAG TTCGCGACAA CGATGTCCGT 80521 GATCCCGAAC ACGGTCTTCT CGGGGACCGT GTACGTCCCG GTCCTGGACT GTCCCGCTCC 80581 CGACCTCAGG TCGATGGTGG CCGAGCTCTG CCGTCCCCCG CCGGTCGCGG TGCCGTCGCC 80641 CGTGCCGGCC GAACCGTCGT CCCCGCCGCC CGCTCCACCG CCCGATCCCG GCTTCTGGCT 80701 GCTGCCGCCG GACGGCCGGC CCGGGCCGGG GGAGGAGCCG TCCGAGCCGC TCTCCGTCGG 80761 GACCGGGCGG GGCTGCACCG CCTGGGTGGC CGCCTCCTCG GCGGCGCTGC GCACGGCCGG 80821 CCGGACCAGC GTGAACCAGG CGATCAGCAG CGCGATCAGC GCCGCGAGCA GCAGGAGCAG 80881 CCACTTGGGG AAGACCGGTA TCTGGACGAA CTCCGCGTCC AGCGTCGGCG CCGTGTGGGG 80941 CTCCTCGGCG CGGTCCTCGG TCTGCTCCGG CTCGCCGGTC TCGCGGGCGT CCACGGTGAA 81001 CGGCCAGACC ACGGGGTCGC CGAACCACAC CGGGCTCGCG GTGCGGACCC GCAGCCGGAG 81061 TTCCTTCGAC TCGCCCGGCT CCAGCGCCGG CTCCGCCGGC GTGAAGGCGA ACCGGAGCTC 81121 CTCGCCCGCC TGCCCGGGCG TGAACCCCAC CCGTACCGGG GTGTTGCCCT GGTTGCGGAC 81181 GGCCAGCAGA TAGCGGCCCC GGAGCCAGCC GCGCCGGCGG CGCGGCGAGA GGTCGGTCCG 81241 CAGCTCGTGG AACGCGCCGA CGCGCACCAC GGTCTCCAGG ACCTTGACCG ACTCGGGCTG 81301 CTCGTTCGGG AGGATCCGTA CACCGAGGGG CAGCTCGCCG GCCCGTGTCT CCGGCGAGCG 81361 CGGCGGTGCC AGACGGAGCG TCACCGTCTC GGACGTGCCG GGATAGAGGG AGAGCCGCTC 81421 GGGCTCGACG GTGGTCCATT CGGCACCGTC ACCGACGACC TTCAGGTCGT ACGCCTCGAC 81481 GATGTCACTG TCGTTGCGGA CGGTCAGGGT GGTGGTGGCG ATGTCGCCCG GCGTCACGGA 81541 CACGGCCGGG ATGTCGAGGC CGGGCGCACC GGGACCGGAG GAGGCTGCGG AAGGCGTCAC 81601 CCGCCCCACC GTAGGAGACC TGACAGATCC GTACGAGGCA CGCGAGGGCA ATGTCCGGGC 81661 AGCTCGGCTG CCCGGCAAGC ACAAGTCAAC TCTCCGGTAA CAATGGATTT CTAGTCTGGA 81721 GAGCCGCCTT CGGCACACCA CCGGCCCGTG GTCGGCTCGT GTCGTGTCCG CCTTCCCCCC 81781 ACCGACCCAG GAAAACAGGT ATCCGATGTT CCGCACCGAG GAGAAGAGGC CGGTCGCGAC 81841 CGGCACTACG GCGCATGACG CCGTCCGGGG CCACCCGGAC GCCCATGCCG CCGGCTTCGG 81901 CCGCCCGCGC CGCGTCACCG TGGCGGTCTA CGCCGCCGAC CCCGTGCTGC GGGTCGGCGT 81961 CGTCCAACAG CTCCGCCAGC GCCCCGAGAC CGAGCTCGTC GACGACGCGG ACGCGGAGAA 82021 CGCGCAGGTC TCCCTGGTCG TCGTCGACGC CCTCGACGAC GACGTGACCG CCCTGCTGAC 82081 CCGGCTGAGC TACAACGGCG CCACCCGCGC GGGACTCGTG ATCGGCACCC TCGGCGTCGG 82141 GGCGCTCCAA CGCGTCGTCG AGTGCGGGGT GTCGGCGGTG CTGCGCCGCG CCGAGGCCGA 82201 CCAGGACCAG CTCGTCCAGC TGGTCCTGGC GGTGGCCAAC GGCGAGGGCG TGCTCCCGGG 82261 CGACCTGCTC GGCGAGTTAC TGGGACACGT CGGCAGCCTG CGCCGCGCGG CCCTCGACCC 82321 CGGCGCCCTG CCCCTCTCCA CCCTCACCAG CAGGGAGGCG GAGATGCTGC GCCTGGTCTC 82381 GGAGGGCCTG GACACCGCGG CGATCGCCCG CAAGACCTCG TACTCCGAGC GGACCGTGAA 82441 GAACGTCCTG CACGAGATCA CCACCCGCCT CCAACTGCGC AACCGCGCCC ACGCCGTGGG 82501 CTACGCGCTC CGCAACGGGC TGATATGACC GTCCCGTCCG GACCGCGGCC CGGCGGCCGG 82561 CGCGACAGCC GGAGGGAAGG CGGCGCTGCC CCAAAGTGCA TCCCGCCCTT CCCCCGGGTG 82621 CGGCCCCCGG GCCCTCCCGC CGCGTGCGCC GCCGCCGCAC GATGACGGGG GGCACCTCCC 82681 GGTGCCGCAC CGGACGGAGA AGGGCACCGT GATGAAGACC GCTGGCCCCG GTGGACGGCA 82741 CCGCCGGGGG AGACTCGCCT CGGCGCTCCT GCTGCTCGTC CCCCTGCTGG GCGCGACGGG 82801 CGTGGCCGGG CCGGACGACC CCCGGACCGC GGCGGCCGCG GCGGACGCCG CCGAGACCAC 82861 CCGCATCGCC TACGCGGGCA CCGGCCACCG CAGCCTCGGC GAACCGGCCT CCACCGACTC 82921 CAGCACCCCG CTGTTCGGAG CGGGACCCAC CCACTACGAC ACCGACCCGT CCGCCCTCGG 82981 CGACCGGCTG GTCTTCGCGA GCCGCCGCGA CGAGAAGCAC CCCCAGATCT ATCTGCGGGG 83041 CGCCGACGGC GGAGTCCTGC GGCTCACCAG CGGCCTGGAC GCGGCCCGTC CCCGGCTCAC 83101 CCCGGACGGC GGGTCGGTGC TCTTCGACGC CGCCGACCCG GCCGGCGGCT CCCAGCGCGA 83161 CCTGTGGCTG GTGCGCACCG ACGGCACCGG GCTGACCCGG CTGACGGACA CGCCCGCCAG 83221 CGAGGAGGAC CCGGCGGTCT CCCCCGACGG CGCCCGGATC GCCTACTCCA GCGACGCCGA 83281 CCCCCTGGCC GGGCGGCAGA TCTACGTCCG CGCCCTCACG GGCGGCATCC CCACCCGGCT 83341 CACCGACCCG GCCCGCGGCA CGGCCTCCGA GCCCGCCTGG AACCCCGTCG ACGACGACGT 83401 CAACCGCGCG TGGATCGCGT ACACGTCGAC CACGACCGAG GACGGGCGGA CCAGGCAGCG 83461 GCTGCGGATC ACCGACGGCA CCACCGACGA GACCCTGTTC ACCGGCGCGT ACGCGAACTG 83521 GCAGGGCCAC GGGGCGGCAT GGCTGCCCGA CGGGGACGGG ATCGTGTTCC TCAGCCCCGA 83581 GACCACCTGC ACCTGCAGGA CCCCCTACGA CCACGTCTTC CGGTCGGTCG TGCACGCCGA 83641 CCGGGAACCC TCCCTGGTGC TCGACGAGGA CCGCGACGTC CTCTCGCCCA CCTGGATCGG 83701 CACCGCCGAG GGCGGCCACG CGATCGTCGA GCGCAGCTCG GCGGCGACCG CGCACACGGC 83761 GACCCTCCAG GACATCCGCG CGGACGGTTC CGACCCGCGC GACCTGCAGC GGAAGATCCT 83821 GCGCGAGGAC CCCCAGGCCG ACACCAACAC CGACCCCGCC AAGGATCCGC TCTTCCAGCC 83881 CGCGCCCCCG TTCGACCCGT GGACCGAACG GCAGAACTAC ACCCCCGACG GGCGCCGCCT 83941 CGTCCTCACC CGCTTCGAGG GCCCCGACGA CGCGCGGATC GAGCGGATCT GGACGGCCGA 84001 CGCCGACGGT ACGAACGAGG CGCCGATGCC CCTCGACGGG CGCGGCGCGC GGGACTGGGA 84061 CACCGACCCG ACGTTCTCCC CGGACGGCAC CCGCCTGGCC TTCACCCGCA CCTCGCCCGG 84121 CGGGGTCGGC GAGGCCGCGG GAGACAGCCG CATCCTCCTC GCCGAGGTCG CCACCGGCCG 84181 GATCACCGGA GAGATCGTGC CCCCGGCCGG TGAACTCCGC GGCGGGGACG CCCAGCCGAC 84241 CTGGTCCTCC GACGGCACCA CCCTGGCCTT CACCCGCGCC CGGCAGATCG CCGGGGGCGG 84301 CGGCAGCAAG CACGTGTGGA CCGCGTCCAC GGCTGACCTG ACCCGGCAGC GCGACCTGAG 84361 CGCGACGCAC TGCCCGCGCG ACTGCGACGT CATCGACGAC AGCCCCGCCT TCTCGCCCGA 84421 CGGACGCTCC CTCGCCTTCA ACCGCAAGAA CGGCGGCGGG CGGATCGACG AGCGCAACGG 84481 ACTGCTCCTG ACCACCCTGT CCGGCGACGC CTGCCAGGTC CTGCTGCCCA CCGCCGCCCG 84541 CGGCCAGGAC GGCGCGTGCG AGCGGGAACT GCCGGACACC ACGCTCACCG GTCCGCACCA 84601 GCCGCGCGAC GCCGCCTGGA CCGCCGACGG CAAGAGGCTG GTCTTCAGCT CCCGGGCCGC 84661 GGCCGCGGTC AACAGCCCGG AGAAGCTGAA CGTCCTGGAC GTCGGCTCCG GTGACATCAC 84721 CCCGCTCACC GCCGAGCTCG CCGGACGCCA GAAGGAACCC ACCGTCCAGC AGTCCGTGGA 84781 CCTCGCCGTC GAGGCACCCG CCACGACGCC CGACGTCACC GTCGGCGCGT CCGGCACGGT 84841 CACCGTCCAC GTGGTCAACC ACGGTCCCGC CGCCTCGCCC GGCACCCGGC TCACCGTCGT 84901 CCCGCCGTCC GGTGTGCGGA TCACCGGGAT CGAGTGGCCC GGCGGCACCT GCGACGCCGC 84961 CTCCCTCCAG TGCGACCTGG GCGTCGTCGA GGCCGGAGCC CAGGTCCCCG TGGACGTCAC 85021 GCTCACCGGC GTCACCGCCG GCGACGCACC CGTCGACTGG TCGGTCACCG GCGCCGTCCT 85081 CGACCCCCGG CCCGGCGACA ACGACGGCCG GAGCGTGATC CCCGTACGCG AGGCACCCCC 85141 GACGCCGACC CCCACGCCGA CGCCGACCCC CACGCCCACC CCGACCCCGA CTCCGACGCC 85201 GACCCCCACC CGGACCCCGA CGCCCACCCC GACTCCGACC CGGCCCCCGC AGCCCCCCGC 85261 GCCGAAGGCC GGACCCGGGG TGCGGATCAC CGTCCAGCCC GAGCCCGGCT ACGTCGGCGG 85321 ACGCGTCGTC GTCACGTACA GCGTCCGCAA CGGCCGCAAC GCGCTCGCCA CCGGACTCCG 85381 GCTCAGGATC GGACTGCCCG CCGGGGTGCC CCACGGCGGA CTTCCGGCGG GCTGCGACCG 85441 GAACGGCGCG TGCGCGCTGC CCGACCTCAC CCCGGGCACG ACCGCCGTCC TGCGGGTCGT 85501 CCTCAGCCCG AAGAAGGCGA TGACCGCCCG CGTCACGGCC GTGCTCGACA CCACCGGCAC 85561 GGACGCCGAC CGCAGCGACA ACACCGCCCG GGAGCGGCTG CGCGTCCTCC AGCCGCGCAT 85621 CGTCGCCGTG CCCGACATCG GCAAGCCCGG ATTCGTCACC TCCGTCCGAG GCGTGGACTT 85681 CCCGCCCGGC GTCCCGGTGC GCTTCAGCTG GAACCCCGGG ATCACCGCCG CCGCCTCGCC 85741 GACCTTCCCG GAGGCCGACG GCACGTTCAT CGGACAGCTC CTCATCCTCG CCAAGGACCA 85801 GACCGGGCCG CGCACCATCA CGGCCTCGGG CCCCGGATTC TCCCCGGTGA AGACCGACTT 85861 CCTGGTCGTC AGCGGCACCG TCCAGCCGCC GGACGGGGTG ACTCGCCGGT GATCC

Example 2 Construction of a “Clean” Host Strain, S. fradiae K159-1

[0102] This example describes the preparation of the clean host, Streptomyces fradiae K159-1, a strain in which the tylGI, tylGII, tylGIII, tylGIV, and tylGV genes have been deleted. Plasmid pKOS159-5 was first constructed as follows. Two fragments flanking the tylG genes were PCR amplified from S. fradiae genomic DNA using the following primers:

[0103] tylGI left flank:

[0104] forward 5′-TTTGCATGCGATGTTGACGATCTCCTCGTC [SEQ ID NO:_];

[0105] reverse 5′-GGAAGCTTCATATGTTCTCTCCGGAATGTG [SEQ ID NO:_];

[0106] tylGVI right flank:

[0107] forward 5′-TTAAGCTTTCTAGAGAGGAGAGGCCGTGAAC [SEQ ID NO:_];

[0108] reverse 5′- AAAGAATTCGAACTCGAGCACGGACTCGTTG [SEQ ID NO:_].

[0109] The Sph I, Hind III and EcoR I restriction sites are underlined. The two fragments were then cloned into pSET152 using the underlined restriction sites and corresponding sites in pSET152 [see Bierman, M., Logan, R., O'Brien, K., Seno, E. T., Nagaraja, R. & Schoner, B. E. (1992). Plasmid cloning vectors for the conjugal transfer of DNA from Escherichia coli to Streptomyces spp. Gene 116:43-49]. The resulting plasmid was named pKOS159-5. This plasmid no longer contains the int-φC31 gene and attP locus from pSET152 and therefore serves as a suicide vector for delivery by homologous recombination.

[0110] Spores of S. fradiae 99 (Russia) were prepared by harvesting from strain grown on 1-2 AS-1 plates [see Wilson, V. T. W. and Cundliffe, E. (1998). Characterization and targeted disruption of a glycosyltransferase gene in the tylosin producer, Streptomyces fradiea. Gene 214: 95-100], filtering the spores through sterile cotton, and resuspending in 1 ml of 20% glycerol [see Hopwood, D. A., et al. (1985). Genetic Manipulation of Streptomyces: A Laboratory Manual. The John Innes Foundation, Norwich, UK]. Spore suspensions were stored at −20° C. A 20 μl aliquot of the spore suspension was added to 5 mL of 2×YT and incubated at 30° C. with shaking. After two days, the cultures were diluted 1:50 and incubated at 30° C. with shaking for 3 h. After that 1 mL of the cultures were collected by centrifugation (recipient cells). Donor cells were prepared by transforming E. coli S17-1 with pKOS159-5 and selecting for apramycin resistance only. Several colonies were picked off the primary transformation plate and used to inoculate 5 ml of LB with chloramphenicol (10 μg/ml) kanamycin (100 μg/ml) and apramycin (60 μg/ml). The cells were grown at 37° C. for 4 h (OD₆₀₀ of 0.4-0.6), collected by centrifugation, washed in 5 mL LB, centrifuged, and resuspended in 100 μl of LB. Conjugal transfer between the donor and recipient cells was performed by resuspending the recipient cells in the 100 μl donor suspension and spreading the cells on AS-1 plates. After incubated at 37° C. for 16-20 h the plates were then overlayed with 3 mL of soft nutrient agar containing 1 mg nalidixic acid and 1.5 mg apramycin. Exconjugants were observed after 48 h of further incubation at 30° C.

[0111] Apramycin resistant colonies were analyzed by PCR to confirm single crossovers at both flanking regions. One colony was selected for carrying out a double crossover as follows. The strain was grown on AS-1 plates non-selectively until well-sporulated. Spores were harvested, dilutions were plated on AS-1 plates, and single colonies were screened for loss of apramycin resistance. A single apramycin sensitive colony was isolated which did not produce tylosin. The double crossover was confirmed by PCR. This strain was named S. fradiae K159-1.

[0112]Streptomyces fradiae K159-1 was deposited under the terms of the Budapest Treaty with the American Type Culture Collection, 10801 University Blvd., Manassas, Va., 20110-2209, on Mar. 12, 2003, with accession number PTA-5060.

Example 3 Construction of S. fradiae K159-1/244-17a, A “Clean” Host Expressing Methoxymalonyl Biosynthetic Enzymes

[0113]Streptomyces fradiae K159-1/244-17a is derived from strain K159-1 (Example 2) by addition of the fkbGHIJK genes from Streptomyces hygroscopicus var. ascomyceticus ATCC 14891, which encode proteins catalyzing the biosynthesis of methoxymalonyl-ACP.

[0114] The putative methoxymalonyl-ACP biosynthetic genes from S. hygroscopicus ATCC 14891 (fkbGHIJK) are arranged with the 3′ end of fkbG (encoding an O-methyl transferase) overlapping by 6 codons the 3′ end of fkbH (encoding an unknown function), which is the last gene of a convergent operon that begins with fkbB (one of the PKS genes) and ends with the genes fkbK, J, I and H. To facilitate expression of these genes in S. fradiae, an operon was constructed beginning with fkbK and ending with fkbG, all in the same direction. This was done using PCR to clone fkbG with flanking restriction sites to allow its 5′ end, with its existing Shine-Dalgarno sequence, to be fused to the 3′ end of fkbH. This operon was then placed behind the tylG promoter in a pSAM2-based vector, which was introduced in S. fradiae clean host K159-1 by conjugation. Exconjugants were selected and named K159-1/244-17a.

[0115]Streptomyces fradiae K159-1/244-17a was deposited under the terms of the Budapest Treaty with the American Type Culture Collection, 10801 University Blvd., Manassas, Va., 20110-2209, on Mar. 12, 2003, with accession number PTA-5053.

Example 4 Construction of an Operon Containing All Five Chalcomycin PKS Genes and Expression in S. fradiae

[0116] A construct comprising the genes encoding chmGI-Vwas constructed as follows: The 3′ end of ChmGV was obtained by PCR with pKOS146-185.10 as the template and the following primers (Chalco-1A: GACACGGCCGGTGAGAGCAGC [SEQ ID NO:_] and Chalco-1B: CTTCTAGATGTCGCGGTGTACGG [SEQ ID NO:_]. The 942 bp PCR product was digested with NcoI and XbaI, the 309 bp fragment was gel isolated, and the fragment ligated into the same sites of Litmus29 to give pKOS342-33. That plasmid was cut with NcoI and XhoI and ligated to a 2.4 kb NcoI-XhoI fragment from pKOS146-185.10 to give pKOS342-35. That plasmid was digested with BglII and XhoI and ligated with a 6.4 kb BglII-XhoI fragment (including chmGIV and the 5′ region of chmGV) from pKOS146-185.10 to create pKOS342-36 (containing chmGIV and GV).

[0117] A 5.4 kb HindIII/ PstI fragment containing the 5′ half of chmGIII was isolated from pKOS146-185.1 and a 6.3 kb PstI/BglII fragment containing the 3′ half of chmGIII was isolated from pKOS146-185.10. These two pieces were ligated into Litmus28 cut with HindIIl and BglII to obtain pKOS342-38. Plasmid pKOS342-36 was cut with BglII and SpeI, the 9 kb fragment was gel isolated and the fragment ligated to the BglII and SpeI sites of pKOS342-38 to obtain pKOS342-39.

[0118] Plasmid pKOS232-172 (described in Example 5), containing chmGI and GII was cut with NdeI and HindIII and the 19 kb fragment was isolated. Plasmid pKOS342-39 was digested with HindIII and SpeI and the 20 kb fragment was isolated. These two fragments were then ligated into the vector portion of an expression cosmid, pKOS244-20 (gel isolated 8 kb NdeI-SpeI fragment). The resulting plasmid (pKOS342-45) was recovered using in vitro λ phage packaging (Stratagene) and infection of E. coli DH5α. The correct clone was identified by restriction enzyme analysis and the plasmid was moved into E. coli DH5α/pUB307 and conjugated into S. fradiae.

[0119] Expression of PKS genes in S. fradiae (in this and the following examples) were under the control of the tylosin PKS promoter (tylGIp, see Rodriguez et al., “Rapid engineering of polyketide overproduction by gene transfer to industrially optimized strains” J Ind Microbiol Biotechnol).

[0120] Apramycin resistant colonies were obtained, shown to secrete bioactive compounds, and grown vegetatively in 5 mL TSB medium (+30 μg/ml apramycin) at 30° C. for 48 h. Two mL of seed culture was inoculated into 40 ml Russia (R) medium (15 g/L whole wheat flour, 10 g/L corn gluten hydrolyzate (Sigma), 25 g/L beet molasses, 2.5 g/L brewer's yeast, 1 g/L (NH4)2HPO4, 1 g/L NaCl, 2 g/L CaCO3, and 34 g/L soybean oil) in 250 ml baffled shake flasks. After a 7 days growth at 30° C., the culture broth was analyzed for 16-membered macrolide production by HPLC (Metachem Metasil Basic column, 4.6×150 mm, 5 μm particle) using linear gradient from 15 to 100% organic phase (56% methanol, 5 mM ammonium acetate) at 1 ml/mm over 7 min. The HPLC used simultaneous detection by electrospray mass spectrometry (Turbo Ionspray source) and UV absorption at 282 nm. LC-MS analysis of the broth showed that several chalconolide derivatives were produced. The most abundant compounds were purified and shown to have the structures below. The 3-keto also forms the enol tautomer.

Example 5 Construction of Streptomyces fradiae K232-192 Expressing a Hybrid Chalcomycin-Spiramycin PKS

[0121]Streptomyces fradiae K232-192 is derived from strain K159-1/244-17a (Example 3) by addition of hybrid chalcomycin-spiramycin PKS genes, which encode proteins catalyzing the biosynthesis of 14-methylplatenolide. The chalcomycin genes were obtained from cosmid pKOS146-185.1, which was deposited under the terms of the Budapest Treaty with the American Type Culture Collection, 10801 University Blvd., Manassas, Va., 20110-2209, on Feb. 19, 2003, with accession number PTA-4961.

[0122] The first two genes of the chalcomycin PKS were isolated from the cosmid pKOS146-185.1 as EcoRI/XhoI and XhoI/BspHI fragments, and a coding sequence for a spiramycin PKS C-terminal linker attached to 3′ end. The EcoRI site is near the 5′ end of chmG1. The EcoRI/XhoI fragment was cloned into a modified Litmus28 with a synthetic linker inserted in order to create an appropriate translation start sequence. The altered region of the Litmus28 polylinker between the AflII and EcoRI sites in this plasmid (pKOS232-165) is given below. The plasmid with the chmG fragment was pKOS232-168A. AflII      PacI   SD      NdeI       EcoRI CTTAAGGGTTAATTAAGGAGGACACATATGTCCGGAGAATTC [SEQ ID NO. _]                          M  S  G  E  F

[0123] The XhoI/BspHI fragment was ligated between the XhoI and NcoI sites of Litmus28 to give pKOS232-156. The two fragments were then joined to give pKOS232-172.

[0124] Starting with overlapping cosmid pKC1306 (described in U.S. Pat. No. 5,945,320 to Eli Lilly Company), a cassette containing the last three ORFs of the spiramycin PKS was constructed as follows. An AvrII site was introduced at the 3′ end of srmG5 by PCR from a natural MluI site to the 3′ end. The PCR product was cut with MluI and AvrII, gel isolated and ligated into a Litmus-based vector (pKOS232-75B) between the same sites to give pKOS231-118A. The 7 kb BamHI/MluI fragment from cosmid pKC1306 was subcloned in Litmus38 (New England Biolabs) to give pKOS231-113A. The 3.8 kb BamHI/MluI fragment of pKOS231-118A was gel isolated and ligated with the 7 kb BamHI/MluI fragment of pKOS231-113A to give pKOS231-120. The 7 kb BsrGI/BamHI fragment from pKC1306 was subcloned in Litmus38 to give pKOS231-113B. The 6.2 kb PstI/BamHI fragment from pKOS231-113B was cloned into Litmus28 to give pKOS231-122. The 7.5 kb BamHI/AvrII fragment was isolated from pKOS231-120 and ligated with pKOS231-122, which was cut with BamHI and AvrII and dephosphorylated, to give pKOS231-124. The 3.1 kb BamHI/SpeI fragment from pKOS231-118B (which contained a PCR fragment that created a 5′ end for srmG3) and the 7.5 kb BamHI/AvrII fragment from pKOS231-120 were isolated and ligated to give pKOS231-130. The 14 kb BamHI fragment was isolated from pKC1306 and subcloned in Litmus28 to give pKOS231-111B. The 14 kb BamHI fragment was isolated from pKOS231-111B and ligated to pKOS231-130 cut with BamHI and dephosphorylated, to give pKOS231-132.

[0125] To attach a coding sequence for a spiramycin PKS C-terminal linker to the 3′ end of chmGII, a HindIII site was introduced at the 3′ end of srmG2 using PCR with PKOS231-112B as template. The engineered HindIII site was positioned with respect to the reading frame to match that of the natural HindIII site in the chalcomycin chmGII gene. The resulting PCR product was cut with HindIII and BamHI (a natural site) and ligated into the same sites of pKOS231-114A to give pKOS232-178. This was then joined to pKOS231-132 at the BsrGI site to give pKOS232-182. The chmG1,2 cassette was isolated from pKOS232-172 as an 18 kb NdeI/HindIII fragment and the srmG3,4,5 cassette was isolated from pKOS232-182 as a 20 kb HindIII/AvrII fragment. These fragments plus a pSET152-based vector having the tylG promoter (the vector portion gel isolated from pKOS244-20) were joined in a three-piece ligation and recombinants were recovered by in vitro lambda phage packaging and infection of E. coli. Correct constructs were identified by restriction analysis (pKOS232-184A) and transferred into E. coli DH5α/pUB307.

[0126] The resulting E. coli DH5α/pUB307 cells were conjugated with S. fradiae K159-1/244-17a (Example 3) to produce Streptomyces fradiae K232-192. Streptomyces fradiae K232-192 was deposited under the terms of the Budapest Treaty with the American Type Culture Collection, 10801 University Blvd., Manassas, Va., 20110-2209, on Mar. 12, 2003, with accession number PTA-5052. Conjugation was performed as described in Practical Streptomyces Genetics (Kieser et al., 2000) except that plates were left overnight at 37° C. before overlaying with the selective agent (apramycin and naladixic acid). Apramycin resistant exconjugants were streaked for single colonies and a set of clones were patched onto R5 plates and inoculated into tryptic soy broth (40 ml in 250 ml shake flasks). Both the solid and liquid media contained apramycin (to select for pKOS232-184A) and kanamycin (to select for pKOS244-17A). Liquid and solid cultures were grown at 30° C. Agar plugs taken from most patches on R5 showed bioactivity when placed on an M. luteus test lawn. The agar was extracted with ethyl acetate and found to contain a compound of 730 amu. TSB seed cultures at 2-3 days were used to inoculate fermentation media and these cultures were grown for 7-10 days at 28° C. Upon extraction with ethyl acetate the 730 amu compound (730-I) was isolated and its structure verified by NMR as shown below. In addition, LC-MS analysis of the filtered culture broth showed abundant production of a 586 amu and a 730 amu (730-II) compound, and a 714 amu compound and a smaller amount of a 904 amu compound (most likely representing 14-methyl-platenolide with all three sugars attached). Thus, the chalcomycin-spiramycin hybrid PKS synthesized the predicted 14-methyl platenolide.

Example 6 Construction of Streptomyces fradiae K344-51 Expressing a Hybrid Chalcomycin-Spiramycin PKS and the chmH Gene

[0127] The chmH gene was cloned from cosmid pKOS146-185.1, which was deposited under the terms of the Budapest Treaty with the American Type Culture Collection, 10801 University Blvd., Manassas, Va., 20110-2209, on Feb. 19, 2003, with accession number PTA-4961.

[0128] A 6.3 Kb EcoRI fragment containing the chmH gene and a small downstream ferredoxin gene was cloned from cosmid pKOS146-185.1 into Litmus28 to give pKOS344-10B. This was then cut with SacI and religated to give pKOS344-016 having a 2.1 Kb insert. An NdeI site was introduced at the start of translation and an internal NdeI site was simultaneously replaced with a PstI site (without changing the amino acid sequence) in a three-piece ligation using two PCR products ligated between the EcoRI and BamHI sites of pKOS344-016 to give pKOS344-022B. The unique FseI site in pKOS344-022B was changed to an XbaI site with a synthetic linker and the chmH gene plus ferredoxin gene were excised with NdeI and XbaI and ligated into the expression vector, pKOS342-108D, between the NdeI and AvrII sites to give pKOS344-037B. This vector was transferred into DH5α/pUB307, and conjugated into K232-192 (Example 5). Exconjugants were selected with thiostrepton and streaked for single colonies to yield S. fradiae K344-51.

[0129] The vector for integration of chmH, pKOS342-108D, uses the int and att functions of Streptomyces phage φBT1. All S. fradiae strains were plated on AS1 agar for sporulation, R5 agar for solid media production, or grown in liquid TSB for vegetative growth and Russia medium for production. All appropriate antibiotics for selection of integrated markers were added to the media, except for the production stage.

[0130] Expression of the chmH gene (with its downstream ferredoxin) dramatically increased hydroxylation of the 14-methyl. A 906 amu compound was detected. This is the structure expected when all post-PKS tailoring of the tylosin pathway occurred, along with an additional reduction adding two hydrogen atoms. The methanol adduct characteristic of the aldehyde is not seen for the 906 amu compound, and reduction of the aldehyde most likely accounts for the addition of the two hydrogen atoms.

[0131] In addition, there appear to be a significant amount of 730 amu (730-I) compound that has the aldehyde and is hydroxylated on the 14-methyl. This is deduced by the presence of the methanol adduct (762 amu) and the fact that the 730 amu compound now elutes later from the C18 column compared with the 730 amu carboxylic acid seen prior to expression of chmH.

[0132] Without intending to be bound by a specific mechanism, FIG. 2 shows proposed pathways for post-PKS modification of the chalcomycin-spiramycin hybrid PKS macrolide product in the absence or presence of ChmH. When ChmH is present, the post-PKS reaction sequence from the Chm/Srm hybrid essentially follows that for tylosin and gives the 904 amu structure, which is converted by reduction of the aldehyde to a 906 amu compound. This reduction of the aldehyde has been described for tylosin (to give relomycin). Knockout of genes for allose biosynthesis or its transfer (tylJ), would give the demycinosyl compound of 730 amu (with the 14-hydroxymethyl and the aldehyde).

Example 7 Expression of a chmGI-GII Operon with the tvlG2 C-terminal Linker in S. fradiae K105-2

[0133] a) Construction of the S. fradiae tvlD Knockout Strain K168-173

[0134] The tylD knockout plasmid was constructed from two PCR products encompassing 1.8 kb regions upstream and downstream of the tyID gene using PCR primers that introduced new restriction sites. The upstream PCR product was cut with EcoRI and PstI and the downstream product was cut with PstI and SphI. These were then ligated together between the EcoRI and SphI sites of pUC19 and the sequence was verified. The resulting plasmid, pKOS168-106, has about 80% of the tylD gene deleted between the artificial PstI sites. This plasmid was introduced into S. fradiae by conjugation from E. coli DH5α/pUB307 and apramycin resistant exconjugants were obtained. Three were found by PCR to be the result of homologous recombination at the expected tylD locus and these were grown in the absence of selection and screened for the second crossover. Apramycin sensitive clones were isolated and some were found that produced demycinosyltylosin (DMT) by LC-MS analysis of the fermentation broths. The strain was designated S. fradiae K168-173.

[0135] b) Construction of S. fradiae tylD K105-2

[0136] The S. fradiae DMT (demycinosyltylosin) producer (K168-173) described above was used to introduce a KS-1 null mutation in the tylosin PKS. The plasmids pKOS168-190 and pKOS268-145 were digested with EcoRI and EcoRV and the 6.2 kb and 2.6 kb fragments, respectively, were gel isolated and ligated together to give pKOS264-65. A mutation was introduced into pKOS264-65 using PCR to change the active site cysteine of the tylosin KS1 to alanine, with the simultaneous introduction of an NheI site, to give pKOS325-8. Finally, pKOS325-8 and pKOS241-52 were digested with PvuII and XbaI and ligated together to give pKOS264-76. Plasmid pKOS264-76 was conjugated into the DMT producer strain S. fradiae K168-173 (Example 5) from E. coli DH5α/pUB307 and exconjugants were selected for apramycin resistance. Clones that underwent the correct first crossover event were identified by Southern blot analysis and one of these was propagated without selection to allow a second crossover. DNA from clones that had become apramycin sensitive was digested with XmaI/NheI and analyzed by Southern blot. Three clones had the pattern consistent with that expected for the desired second crossover to leave the KS1 -null mutation in the chromosome. This strain was designated S. fradiae K105-2, and was shown to produce no tylosin-related structure, but could convert O-mycaminosyl-tylonolide (OMT) into demycinosyl-tylosin (DMT).

[0137] c) Construction of a chmGI-GII Operon with the tylG2 C-terminal Linker

[0138] The tylG2 C-terminal linker region was isolated by PCR from a pSET-based vector encoding the including the entire tylosin PKS (pKOS168-190). The primers used were TylLink-A: 5′-TGAAGCTTCCCGCCACGCTGGTG-3′[SEQ ID NO:_] and TylLink-B: 5′-CGTCTAGACAGGGTGTGAAACCG-3′) [SEQ ID NO:_]. This created a HindIII site at the sane position of the encoded sequence corresponding to the natural HindIII site in the linker region of chmGII. The amplimer was cut with HindIII and XbaI and ligated into Litmus29 to give pKOS342-78. The tylosin linker region of pKOS342-78 was excised using HindIII and XbaI, and then ligated into HindIII and XbaI-digested pKOS232-172 (Example 5) to create pKOS342-82. This hybrid piece was then cut out with NdeI and XbaI and ligated to a pSET-based vector (pKOS232-189) cut with NdeI and SpeI to create the pSET152-based expression vector, pKOS342-84.

[0139] d) Expression of a chmGI-GII Operon with the tvlG2 C-terminal Linker in S. fradiae K105-2

[0140] The expression vector pKOS342-84 was transferred to E. coli DH5α/pUB307 and conjugated into S. fradiae K105-2 (this example, above). Apramycin resistant colonies were isolated and fermented in production medium. The broth was analyzed by LC-MS and found to contain the compound shown below. The chm/tyl hybrids differ from the chm/srm hybrids only by having a 4-methyl in place of a 4-methoxy, apparently making the chm/tyl good substrates for the TylH hydroxylase.

[0141] All publications and patent documents cited herein are incorporated herein by reference as if each such publication or document was specifically and individually indicated to be incorporated herein by reference.

[0142] Although the present invention has been described in detail with reference to specific embodiments, those of skill in the art will recognize that modifications and improvements are within the scope and spirit of the invention, as set forth in the claims which follow. Citation of publications and patent documents is not intended as an admission that any such document is pertinent prior art, nor does it constitute any admission as to the contents or date of the same. The invention having now been described by way of written description, those of skill in the art will recognize that the invention can be practiced in a variety of embodiments and that the foregoing description are for purposes of illustration and not limitation.

1 62 1 85915 DNA Streptomyces bikiniensis 1 ggggcccgcc ggacggggct gcccggctct cggcggtgcc cggtgggccg ggtgcgggct 60 cgcccgcggc gagatgctcc aggacctccg ccagttcccg gcaggcgcgg cgtaccgagc 120 ggcgggtcgc acgctgctcc gtgatgacgg aggcgagaag cagggcggtc agtgcggcgg 180 aaccgttgaa cgcctggagc ttggccatga tctcgacgtc cgagaggtgg aggaaccctc 240 cccgtccggc gttcgcctcg aaggtggcga gcacggaggc gaagagcgcg cagagcatgc 300 ttccggtgag ctggaagcgg agcgccgccc agatcagcag ggggaagacg aggaagagca 360 tgcccaccgg gctgagcacg gccatgggca tgaggatcag ggtcgcgaga cccagcaggg 420 ccgcctcctt ccagcgccgt acgcggaacc gtccggccgg ccccgcgagg acgaggagga 480 gcggggcgac gagcagcacc cccatcgtgt cgcccaccca ccaggccagc cagacgggcc 540 agaactcggt cgtgtccagg gagctcttcg ccacctgcag tccgaccccg gcggtcgcgc 600 tgatcagcat ggcgccgaac ccgccgagga agaccaggga gagtccgtcc cgcagccgtg 660 ccatgtcgag ccggaagccg gcccgtgtca gcagcaggaa ggcgcagagc ggcgcgacgg 720 tgttgctgac cacggtgacc acggtggtgg gccccggcgt ggtgagggag gcgatgacga 780 ggaaggagcc gagggcgatc ccgggccaga cgcgcgcgcc gagcagcagc agggcggcga 840 cggcgacgcc ggtgggaggc cagatggggg tgaccaccac gccttcgacg acgaggcggc 900 ccatcaggcc gagtcgtccg gccgcgtagt agagcaccgc cacggccagc gacatcagcg 960 ccgtcgccgc gggggaccgg tactgccgaa tatccaacac gtctgccatc agacaccgac 1020 cgggttgccg cgcccctgca tggccgcctg cgtgtcgggg acacgccgcc cggcccggac 1080 cgggccgcgg ggaggaccgg cccgaggcgg gtcccctcgc tcactccccg gtcgccggcc 1140 ggggcggacc gccgtcgtgg ccgacgacga ggacggccgc gtcgtcctcg tgccccaccg 1200 tggccgccag tcgcatgacg gcggtggcga gcgcgtcgac gtccagcccg gcgacggccg 1260 tgatcccggc gagtctcgtc acccggtcga gaccctcgtc gatgtggagc gagggcccct 1320 ccacgacccc gtcggtcagg aggacgaaga cgccgtcggc ggtgagccgg tggcgcgtgg 1380 ccgggtagtc ggcgccgcgc agcacgccga gaggaggccc gccctcgctg tcgtcgatgc 1440 cggagcggcc gtcggcggtg gcccagatgt gggggatgtg gccggcccgg gcgcattcca 1500 gggtgccggc ggcggggtcg agccgcagga aggtgcaggt ggcgaagagg tcggcgccga 1560 gggagacgag caggtcgttg gtgcggccga gcagctctcc cgggtccgcg gtgacggagg 1620 ccagcgcgcg cagtgccacg cggacctgtc ccatgaaggc ggcggcctcg atgttgtgtc 1680 cctggacgtc gccgatggac atgccgatcc gcccgccagg cagggggaag gcgtcgtacc 1740 agtcgccgcc gacgttgagc ccgtggttgg cgggctcgta ccggacggcc agccgggcac 1800 ccggaagact gggcaggtcc gagggcagca tgccgcgctg cagggccacg gcgagctcga 1860 cacgggaccg ctgcgtctcg gccagctccc gcgccctggc ggtcagcgac ccgagccgga 1920 ccagaaggtc ctcgctgctg tcggccgggc gtctgcggaa catcgatcac tccgacgtca 1980 cgacaatcct cgcatcactc cgtcccgtct ccagcacgcg ggaccacagg ggaccacccc 2040 ggtacgaaca ggtccttccc actgtgcccg gagggggcgg ggtccgcatc tcatcggcgg 2100 gagagcgcgg tggatcccag ggggcccgct caggtcaccg aaaacgagca aacgttcgat 2160 aatgtggtcg cgccggtctg tgcggccgtt cagcgttcga cggtcactgc ggcggccgcg 2220 atgccgtcgc gcaccagcca ccggccggtg aacccgccca gctgccgtcc gtcgaccgtc 2280 ggcccgggca cgagcagccg ggccctgaaa cggccgcccg gctggaagtc gacggccgcc 2340 tccccgaagt cgagccggct ccgggtgagc gggaaccacg ccttgtagac ggcctccttg 2400 gcgcagaaca gcagcctgtc ccacgggatg ccgggccggg ccagtgccag agcggccagc 2460 ggcccgcgct catccgcggt cgtcaccgcc tcgaagacgc cgtgcggcag cggaagggcg 2520 ggctcggcgt cgatgcccag agacgccacg tccgcctcgg acgccaccgt cgcggcgcgg 2580 tagccggcgc agtgggtcat gctgccgacg acaccgggcg gccatcccgg cgcaccccgc 2640 tcaccgggca cgagggccac cggcccccac cccagaccgg ccagcgcgcg tcgcgcgcag 2700 aagcgcacgg aggtgaactc cctgcgtcgc ttgtcgaccg cgcgcccgat cgccttctcc 2760 tcgtcggcga acagccgcgc ctcggggtac cggtcggcat ccaggacgtc gccgaagacg 2820 tccaccgaca ccgcggcggg cggcagcagt gcgcagatca gcccggccca ccgcggcacc 2880 gacacggcgg cgtcggcctc ggcacggtcg tgcacgcacg ccgacgccgc ggcgtcggcg 2940 agggggcccg tgcggctgcc gtccccggac cgccgcgccg aggacgccgc cggcgggaag 3000 ccgtccctca cacgggcacc gtggcgtcgt cgtgcgtgcg tccgagcgcg ttcagccggg 3060 ccagctggcc atcggagaga gcgatgcccg acgccgcgac gttctccctc agatgcgcgg 3120 gcgagctggt gccggggatg ggaatgaccg ccggcgagcg gtgcagcagc cacgcgagcg 3180 ccacctgacc ggccgacacc tccagctcgg tggcgatgtc ggccaccggg ctccccccgg 3240 cggcgagcgc accgcgggcg atcggcagcc aggcgatgaa cgcgatctcg tgcttctcgc 3300 agtactcgac cacctcgtcg ttgcgccggt cggtcaggtt gtacacgttc tgcacgctgg 3360 ccacggtgat gtgctcacgg gcggcctcca cttcccggac ggtgaccttg gacagcccga 3420 tgtgccggat cttcccttcg tcctgcagtt ccccgagcgc accgaactgc tcggccgccg 3480 gcaccttcgg atcgatccgg tgcagctgga agaggtcgat gcggtcgagt cgcagcctgc 3540 gcaggctcag ctcggcctgc tggcggaggt actccggtcg gccgcacggc acccactggt 3600 cgggacgggg ccggcactgt ccggccttcg tcgcgatcac gaggccgtcg gggtacgggc 3660 gcagtgcttc ggccagcagc tcctcgttgc ttcccagccc gtaggaatcg gccgtgtcga 3720 tgaaggacac accgaggtcc acggccagcc gggccgtgct gatcgcagcc tcccggtcct 3780 ccggcgggcc ccagtacccc ggaccggtca gccggagggc gccgaaaccc aaccggtgta 3840 ccgagaggtc gcctcccaga gggaaggtgg tcctgccggg ctgtgccatg cgttcctcct 3900 ggacgacgtc cgtgcactcg ggtggggcgc gtggtgacct cggtgggggc gggccgatgc 3960 cgaccgtccg aacacggtgg atcccccggt tcagggagcc gtcgtggagg gcacccgctc 4020 gtcggcccgt cgggtcacct cgtgtccccg ctccagagtg agccgcacga tgtcgcagac 4080 ccgacggatg tcctcgcgag agacggtggg gccggtgggc agggcgagga ccttccgcgc 4140 gagccgttcg gtgtggggca gggagaccgg ccgctccgag cggtagggct ccatctcgtg 4200 gcatccgggg gagaagtacc gctggcacat gatgttctcc gccctcagca cctcgtccag 4260 caggtcccgg tggaccccgg tcaccgcggc gtcgacctcc acgaccagat agtggtagtt 4320 gttgcgctcg gcacggtcga actccatgac cttcagcccg gcgagcccgg cgagttccga 4380 ccggtagtcg tcgtggttgg cctcgttccg gcgaaccgtc tcctcgaagg cgtcgagcga 4440 ggtgagtccc atcgcggcgg cggcttcggt catcttcccg ttggtgccgg tctccgtgga 4500 cacccgcccc tgggtgaatc cgaagttgtg catcgcgcgg acccgctggg ccagcctctc 4560 gtcatcggtc accaccgcgc cgccctcgaa ggcgttgacc accttggtgg cgtggaagct 4620 gaacacctcg gcttgtccga agccgccgat cggctgccct tccgacgtgc agccgagtcc 4680 gtgcgcggca tcgtagaaga gcctgagacc gtgatcggcc gcgaccttcg ccagccggtc 4740 gaccgcgcag ggccgacccc acagatggac cggcacgacc gcactcgtac ggggggtgat 4800 cgccgcctcg atcagatccg ggtccaggca gttggtggcc gggtcgatgt cgacgaagac 4860 cggggtcaga cccagccagc ggaacgcctg ggcggtcgcc gggaaggtca gcgacggcat 4920 gatgacctcg cccgacagat cggcggcgcg ggccagcaac tggagggcga cggtcgcgtt 4980 gcaggtcgac acgcagtagc gcacgccggc gagttccgcc acgcgctgct cgaactcccg 5040 ggccagcggc ccgccgttgg tcagccactg gtggtccagc gcccagttca cacggtccag 5100 gaaccgcgct cggtcgccca cgttgggccg ccccacgtga agtggttgca ggaacgccga 5160 cgggccgccg aacacggcga gatcaccgag attgcgtttc atggtcatac ctccccggtg 5220 cacgggacgg tgcacccggc agcagccggc acaggacgtg gacgtaccgg agggacaggg 5280 gccgcagcgc acgacggcgt ctccgtcgtg cgtacgcgaa aggggcgcac ggaacggatc 5340 agtgctcgcg gcgccagtag acgcccgtca cgtccaccgt ctcgatcggc tcgtcgatgc 5400 cgtgttcgct ccggtagtcg tggacggcct gcttgcacgc cgggatcagg tagtcgtcca 5460 cgatcacgaa cccgcccacg gacagcttgg ggtagaggtt gaccagcgcg tccctcgtcg 5520 actcgtacag gtcgccgtcc acccgcagca ccgcgagccg gtcgatcggc gcggtcggca 5580 gcgtgtcggc gaacatgccg ggcaggaacc tgacctgctc gtccagcagg ccgtagcggg 5640 cgaagttctc cctcacctgc tcctcggaac agctcagtac ccagttcagg tggtggaact 5700 ccatcgcccg gtcgagcggg tggctgtcct cggacgtcac cgggacaccg gcgaacgagt 5760 cggcgagcca cacggtgcgg tcctccacac cgtgcgcctt gaggagcgcg cgcatcagga 5820 tgcaggcgcc gccgcgccac acgccggtct cgatgagatc accgggaaca tcgtcctgga 5880 ggaccctctc cacgcacctc tggatgttgt ccaggcgttg caggccgatc atggtgtgcg 5940 cgaccgtcgg cacgtccagt ccttcggccc ggtggtcggc gtcgaaggtc ccgcgctcga 6000 cgtccgggcc ctccgccccc ggacgcatgc ggtccgccag ttccttgtcc aggacgttca 6060 tcccgaccgg gaaggtcggg tgatccccgt agatggtgtt cgacacgacg ttcttcatga 6120 ggtccacgta gagctcgcgg gtctgcacgg tcgacttacc tccggctaga tatcgaacag 6180 agagagaatg tgcggggcga cggcgtccgc ggacgcggtg ggagccgtcg cggtcgggtc 6240 acctcaggaa gccgcgcgcg tcctcccagc cggccacgac atcggcctcc agctggttga 6300 gccgcgccgc caccacctgg tcgaacccgt ccatgaagta ctcgtcaccg gcgtgcggcg 6360 ctatcagacg gccgtcgtcc acgaaccgct cgacgacctc cgtcagggag gtgcccggcc 6420 ccacccggcc cgcgacgtac cggtccgctc cggtgagatc cgggaacccc gcctcccggt 6480 acaggtacac gtcacccagc aggtccacct gtacggacac ctggggatgc gcggaccggc 6540 gcatggttcc gggcctgatc ctgagcagct cggcgtccgc gccggtcttc aggctgtgca 6600 acgcgtagcc gtagtcgatg ttcagcgtgg gggtccgccg gctcaccgcc tcctcgaacg 6660 cgagcagccc ctcctggagt tcggcgcgtt cggcctcgaa cagcctgccg tcctcccggc 6720 cgctgtagtc ctcgcgcacg ttcaggaagt ccaccggccg gtccggcgcg gcctcgttca 6780 ggtcggcgat gaagtcgacg aggtcgagca gccggtggac gcgcccgggc agcacgatgt 6840 agctgagccc gagccggatc gggctctccc gctcggaccg cagctgctgg aagcgccgca 6900 ggttggcgcg gacccttccg aaggcggcgc gcttgcccgt ggtctcctcg tactcctcgt 6960 cgttcaagcc gtacagcgag gtgcgcaccg cgtgcaggtc ccacaccccg ggctgcctgt 7020 ccagcgtccg ctcggtgagc gcgaacgagt tcgtgtacac ggtcggccgc agcccgcgag 7080 ccgccgcacg gctgctgagc gcgcccaggc ccgggttggt gaggggctcc agaccgcccg 7140 agaagtacat ggcgtacggg ttgccggccg ggatctcgtc gatgacggac gcgaacatcg 7200 cgttgccgga ctccagcgcc gacgggtcgt accgcgcacc ggtcacccgg acgcagaagt 7260 ggcagcggaa catgcagctc ggccccgggt acaggcccac gacatagggg aaggccggct 7320 tgtgcgcgag cgccgcgtcg aagacccccc gtcgctccag cggcagcagg gtgttctgcc 7380 agtacttgcc cgccggcccg ttctccacgg cgtggcgcag ctccgggaca cggccgaaga 7440 ggccgaggag ccggccgaag gaggcccggt ccacgtccag catccggcgt gcctcctcca 7500 ggggcgtgaa ggggtggttc ccgtagcgct cggccagccg cacgagccgg cgcgcgaccg 7560 tcgggccctc gtcgacaccg acgcggccgt cggagaccag ggcgcggtgc accgtgtgga 7620 ccgctgccgg caggtcggcg ccggggcggg cgcacagggc gaccggatcg gccgcggtgg 7680 aggcgtgcga ggtcatcctt cgtgtccaat cgtctgcgtc cggagggtcg gtccgttccc 7740 cgggaaacgc ggcggggcgg tcaccgggac ggcaccgtga cggatgtggt cagggacgtc 7800 tcggccgcgg acgggcccac gtgtacggcc ctcctgccgg tgcccggctt ccacgtgccg 7860 gcggcggtgt cccagtagcg cagttgctgc tcgtcgacgg ggacggtgac ccgccgctgt 7920 tctcccggcc ggagggtgac cttggtgaat ccggcgagtt tgcgcagcgc ctggggggcc 7980 tgggtgtccg gacttgcccc gaggtagacc tggacggtct ccctgcccgc ccggtcaccg 8040 gtgttgcgga cggtgaccgt ggcctccagc ccccgggcgg tgcgcgccac ggacaggtcg 8100 ctgtaggcga aggtggtgta cgacaggccg tacccgaacg ggaagagcgg ggccacgccg 8160 gtccggtcgt accaccggta gccgacatcc agtccctcgg aataggtctc cttgccgtcg 8220 acacccgggt agcggtgcgg gtcaccggcc atgggatggc cggtctcggt ggccgggaag 8280 gtctgggtca gccggccgct gggattcgcg tcgccgaaca gcagggcagc ggtggcctcc 8340 gcgccctcct gccccgggta ccacatctcc agtacggcgg ccgtctcacg cagccagggc 8400 atgagcaccg aggaaccggt gttgaggacg acgatcgtgc gggggttgac cttggtgatc 8460 gccgcgatca gctcgtcctg tcggccgggc agggacagcg aggaccggtc cacgccctcg 8520 gcactgtcgt cgtgggcgaa gacgacggcg gtgcgggcct cggccgccgc cgcgacggcg 8580 cggtcgaagt cgtcccgggc agcctcggga gtgacccagc tcagctccac cgacagcggg 8640 gtctgttcga aggcccagcc gttcatggtc accgcgtggg tgccgcgggt cagccgcatc 8700 gtggtggtga cggtgccgaa cgcctcggtg ccgaggacag cggactgccc cgcgatctgc 8760 aggttggcga ccccgccgac ggcggtgaag gcgatcttgt agtcgccgtc ggcggggacg 8820 gtgagccgac cctcgtagaa gacgccctgg ccgctgggat ccagttgctt cccgctcgtg 8880 aaggcggggg tgagcgagct ttcgggcacg ggcacgccga ccaggtcctc accgggctcg 8940 tggacgaccc gggccttctc gccggcgcgc cgtgcgaggg cgtcgacggg tgcggtcgcc 9000 cggtcgggta tgacgtgcgc gctgccgttg ccggtgacct tggggtgctt ggcgctgttg 9060 ccgatgacgg cgatgtccgt ggcgtcctca ccggtcaggg gcagcgtccg gcgctcgttg 9120 cgcagcagca ccccgccgtt ctcggcgatg gtgcgggccg ccgcgcggcc ggcctcggga 9180 tcacgctgcg ggcgctcggt cgccttgccg tcgagcaggc cgaagcgctc catctggccg 9240 aggatgcgga cgacggaccg atcgagcgtc gcctcgggga cgctgccgtc ccgcacggcg 9300 gccctgagcg cggaggagaa gtacttcgat tccggcaccg gctgccccag ggtcagctcg 9360 acgcccagtt cctggtcgag gcccctggtg atgtcgccgg tggcgtgggt cgccagccag 9420 tcggacacca cccagccgcg gaagtcccac tgttcgcgca gcacctcctg caacaggtgc 9480 tcgttcccgc atgcgtgcgc gccgttgacc ttgttgtacg agcacatcac cgaggcggcg 9540 cccgcccgca cggcgctgcg gaaggccggc agctccacct cctggagcgt ctgctcgtcg 9600 accacggcgt cgatggtctc ccgctggtac tcctggttgt tcgcggcgaa gtgcttgacc 9660 gtggccatca ggccctggtt ctggatgccg cggacctcgt gggcggccat ccgggacgac 9720 agcagaggat cctcgctgta ggtctcgaag ttccgccccg cgtgcggcac ccggatgacg 9780 ttggtcatgg gaccgaggac gatgtcctgt ccgagggccc gtccctcccg gcccaggacg 9840 gtgccgtact cctcggcgag gcgttcgtcg aaggtggcgg cgagcgccac gggggtgggc 9900 atggcggtgg cggtaccgcc gagcagacgg atgccgaccg ggccgtcggc ggtgcgcagc 9960 tcggggatgc cgagccgggg cacgcccggc agatagccga tgccggtcat ggtcggcccg 10020 cccacgggcc cggtggtcca gtggacgaac gagatcttct cgtcgagggt catcttcgcc 10080 accagcccgc gcacccgcgc cgtcccgggc tcggcggccg gagcaccggc ggcggagggg 10140 gcggtgagca gaccgccgac gcacagggcc gcgagcgcgg atccgacggt gcgccggatg 10200 cggcgacccg tcctcgtcgt gccgaacagc atgctgacgg acgtcctttc tgccgaggtt 10260 gccgtcctca tcggggcggg aacgtttctg tccgtgccgc catgatcacc agcccacgag 10320 catcgtgcgc gggccccgca ccaccatctc cgtcttccac tcgacgggct gggcgaggtg 10380 cagcccgggg agttcgtcga gcagggtccg cagcgcctcc tggagctcca gccgcgcgag 10440 ggacgcgccg aggcagtgat gcggaccgtg tccgtacccc aggtgccggc cggcgtcgtc 10500 gcgggtgatg tcgagcacgc cgggcgagcg gaagcgcagg gcgtcccggt tggcggcgtt 10560 catctggacc agcaccggat cccccgcccg caccagcgtc ccgcccacct cgacgtcctc 10620 ggtggcgtag cgcgggaatc ccgcctggct gccgagcgga acgaaccgcg tcagctcttc 10680 caccgcgttg tccagcaggt caggacggtc ccggaggagg gccagctggt ccggctgttc 10740 gagcaggacc aggacgaagt tgctgatctg gctggccgtg gtctcgtgcc cggcgaacag 10800 gaggaagacg atcaggtcga ccaactcctc ctgcgacagc cggccctggg cgtcacgggc 10860 ctcgacgagc gccgagacga gatcgtctcg cggcgcggcg cggcgggccg tgatcaggtc 10920 cgccagatag ccggtcagct cgccggccag ccgcacatgg tcctcggcgg tgagcgagct 10980 ggtggacatc gctatctcgc accagccgcg gaacaggtca cggtcctcct cgggcacgcc 11040 cagcaggccg cagatgaccg ccacgggaag ggggacggcg tagtggtcca cgaggtcgac 11100 gggcgatccg agcgccgtca tgtcccggag cagcgacgcc gtcatccttc ggacgtgcgg 11160 ccgcatggcc tccacgcggc gcggggtgaa cgccttggtg accagcccgc gcagcctggt 11220 gtggtccggc gcgtccatgc cgatgatgcc gttgggcgtc cgcagctccc gcatgcgcgg 11280 cgcgtcgttc tccgcctccg cggcgtggct gaaccgccgg tcgccgagga cgaaacgcgc 11340 gtcgtcgtaa cgggagacga gccagcccgg ctccccgtac ggcatgtgga cccagaggag 11400 tccttcgctc ttccgcgcct gctcgtacgc ctcgtccagg tccagtccct ccgggcggcc 11460 gaagggatag gagacgggtg cggtcttcgt gctggtcaag gggagcccca tatcgcgtcg 11520 ttcgggtgct taatcgtcgt gggccggatc atgcggccga gccgccccag gtgacgggga 11580 ccgcctcggg ggtgcgcagg agggagccgg cccgccagcg aagctcactc gcggggacgg 11640 acagccggag ctccggcagg cgctcgacca gggtgctcag cacgacctgc agttcgagcc 11700 gggccagggg ggcgcccatg cagtagtggg cgccgtgacc gaagccgagg tgcgggttct 11760 gggcacgggc caggtcgagg gaggcggcac cgggaaacgc cgtgtcgtcg aggttcgcgg 11820 acgcgatcga ggtgatgacc gcctcgcccg cgcggatgag cgtgccgccg atctcgacgt 11880 cctccaaggc gatgcgggcg aacccgtcca gggtgctcag cggggtgaag cgcagcagct 11940 cctcgacggc ggagggaacc aggtcaggtt cggtcaccag gcgctcgtag aggcggcggt 12000 cgtcgagcag gaggaggacg aaattgccga tctgggtggc ggtcgtctcg tatccgctga 12060 tcagcaggcc ggagcccatc atgaggagct cggcctcgga gagccggtcg ccttcgtcac 12120 gggcctggac catggtgctg aggaagtcgt cggtgggccg ggcgcggcga tcggccacga 12180 ggtcggccat gtaggcggag aagtcctcgg tcgcccgctg cacttcggcg ggccccaggg 12240 aggaggacac cagcgcctcg gagaagtccc ggaagaggtg gcggtcgtcg taggagacgc 12300 ccagcagtcc gcagatcacg gagatcgaca cgggcagcgc caggtcttcc atgacctcgc 12360 cggacggctc gtcgcgcgcg accatgccgt cgagcagttc atcggtgaac cgtgagaccc 12420 gcgggcgcag ttcctccacc cggcgggcgg tgaacgcctt cccggcgagc cgccggagcc 12480 tggtgtgtcc gggcgggtcc atggagatga gaccgccggc gggcagcggg tactcggtgg 12540 gccggggcac gtcacgtccg gccccggcct ccatgctgaa ccgcgggtct cccaggaccg 12600 ccctcacgtc ggcgtgtcgg gtcagcagcc aggcctcacc gccgtacggc atgcggatcc 12660 gggacacggg ctcgtgctcc cgcagacggc tgtagagcgg atccagcgcg atgccctcgg 12720 gcggggagaa ggggtacggg cgagtccggt ggaccggaca gctagacgtc atggacactc 12780 tctcggtcgt acggggcggc ggcagagctc gaagggtgcg ggcggccgac ggcgagcccg 12840 gtcgccgtcc ggatcgtccg gcacaccgct tcggcctgct cggtgaggta gaagtggcct 12900 ccggggaagg aacggaacgc cgtctccccg gtggtcagcc cgtgccaggc cagggctccg 12960 tcggtgggga cgtgcggatc cgcgcttccc gtcagcacgg tgatcgggca ggcgagcgga 13020 gctcccggac gccacgtgta ggtggcggcg gcccggtagt cgttgcggat cgccggcagg 13080 gccatccgca ggacctcctc gtcggccagc acccgggggt cggtgccttg cagttcggcc 13140 agcttggcga ccagccggtc gtcgctcagc aggtgcgcgg tggtccggtg ggcgacggtc 13200 ggggcgacgc ggccggagac gaacagatgc gccagcctgc tctccggcgc ctgttccgcg 13260 agccggcggg cggtctcgaa ggccaccagc gaccccaggc tgtgaccgaa gagcgccacc 13320 ggccggtcca gccaggggcc gagcgctccg gcgacgtgcg tcaccagagc gtcgacggag 13380 tccacgaacg gctccagccg ccggtcctgc cgcccgggat actggacggc gagcacctcg 13440 acccggtccg gcagcagaca ggtgaagggg aggaaggcgc tggcgctgcc gccggcgtgc 13500 ggaaggcaca cgagccggag cgcggggtcg gcgacgggcc ggtagcggcg cagccagagg 13560 tcgccggcgt tggtggagcc gggcgccgtc gtggcgggcc cctcgttcat gcgtgatccg 13620 cttccggacg tcacggtgtc agcgccttcc accacgtgcc gttgtcccgg taccagtcga 13680 cggtctccgc gagcccgcga tcgaaggcga cgcggggagc ccatcccagc tcctcggtga 13740 tcttccgggt gtccacgcag tagcgacggt cgtgcgcggc ccggtccggc acccggtcca 13800 ccacggacca gtcggcaccg aagacgccga gaagacgacg ggtgaggtcg acgttggaca 13860 gttccgtccc gccgccgatg ttgtacacct ctccggcccg cccccgggcg gcgaccatgg 13920 cgatgccccg gcagtggtcg tccacgtgca gccagtcgcg ccggtggagg ccgtccccgt 13980 acaggggaag gcgcaggccc tccagcagat gggtcacgaa gagcgggacg accttctcgg 14040 ggtgctggtg ggggccgtag ttgttggagc agcgcgtcac ccggacgtcg aggccgtggg 14100 tacggtggaa ggcgagcgcc aggaggtcgg aggaggcctt ggacgccgcg tagggggagt 14160 tcgggtccag cggatcggcc tcggtggagg agccctcggg gatcgatccg tacacctcgt 14220 cggtggagac gtggacgaag cggctgacgc ccgcttcgag cgccgaccgc agcagggtct 14280 gcgtccccag cacgttggtg gtgacgaagg cggcggagtc cgtgatcgag cggtccacgt 14340 gcgactcggc ggcgaagtgc accaccaggt cggtgccgcg cagggcctgg gccaccgtgg 14400 gcgggtcgca gatgtcgccg tgcaggaagg tgtgacgggg gtggccggcg acctcggcga 14460 ggttctcggt gttcccggcg tacgtgagct tgtccagcga gaggacgtgg gcgccggcca 14520 gctccggata ggagcccgac aggagctgtc tgacgaagtg cgagccgatg aagcccgctg 14580 ccccggtcac caggacgcgc atccttgatc cgcctttctg ccgtgctgtg tgggggaggt 14640 gtggtcaacc ggtgcgcgtc gccccgagtc ccgaggcgac ctccatgagg tagtccccgt 14700 agctggaggc gctcagctcc tcacccagcc ggtaacaggt gtccgcgtcg atgaagccca 14760 tgcgcagcgc gatctcctcg agacaggcga tgcgtacgcc ctggcgctgc tcgaggagct 14820 ggacgtactg acccgcctgg agcagggagt cgtgggttcc catgtcgagc caggcgaatc 14880 cacgtccgag ctgggtcagc cgggcgcggc cctgctccag ataggacagg ttgatgtcgg 14940 tgatctccaa ctcgcctcgg gctgagggct tgaggtcctt cgccagctcc accacgtcgt 15000 tgtcgtagaa gtacagcccg gtgacggcga ggttggagcg aggacggctc ggcttctcct 15060 ccagggacaa caggtgcccc tgctcgtcga tctcggcgac gccgtagcgc tcgggcgact 15120 tggacggata gccgaacagt tcacatccgt cgagacgtcg cagggagtgc ttcaggacgg 15180 tggagaatcc ggggccgtgg aagacgttgt cgcccagaat gagcgccacc cggtcgttcc 15240 cgatgtgctt gtcgccgacc aggaacgcgt cggcgacacc gcgcggctcg tcctggaccg 15300 cgtagtcgag ctggataccg aggcgcgagc cgtcgccgag catgacctgg aacgtctcca 15360 cgtgctggtg cgaggagatg atgaggatgt cctggattcc cgccagcatc agcaccgaca 15420 gcggataata gatcatgggt ttgtcataaa cgggcaactg ctgtttggaa agcgcaccgg 15480 tcagcggctg cagtcgagtg gcgcttcccc cggcgaggat tatccccctc actccggggc 15540 gtttcagcgg tgtctcgaac acggttggtc ctccgtggtc acatggccga tatggggggt 15600 gaagacactg tcctgagagg ccggcggacc ggctgtcgcc tcgcggacac agcggcttaa 15660 tgcattcacc ccgccccggg accgtcatcc gagaagaagg aatgcggtgt cgtgggaacc 15720 gacgtccagg agttcctttc gggccgcgga acggcggcgc ggagattctg aaccgcgggg 15780 gattccaggg cggtggcagg gaagggaacc accgccgcgc catctctccc ggaacgttcc 15840 gcaagcggcg ggccgtgctt cggacggcct atctctgcgc ctgttgctgt tcctgccagg 15900 cctgataggt cggcagcaga ccgagccgtt cggccgtcgc gagggtcggg gcgttctcgt 15960 ccctgtcgga gagcagcggc tcgatgtcgt ccggccacgc gattccgagg tcggggtcga 16020 gcggattgac ggagtgctcg cgtgcgggag cgtatccgga ggagcagagg tagacgagcg 16080 tggcgtcgtc ggtgagggag aggaaggcac ggcccagtcc cgcggtcaga tagacggcgg 16140 tgttgcgttc cgcgtccatg ggcacgatct cccagcgccc gaaggtcggc gaaccgatgc 16200 ggacgtccac gacgacgtcg aggccggctc cccgcacgca cacgctgtac ttggcctgac 16260 ctggcgggat ctcggtgtag tggatcccgc gcagcgcgcc gcggtgcgac accgcgacat 16320 tgacctgggc caccgggaag tcatggccga acgcctgacg gaagctctcg ccccggaacc 16380 actcgtggga cctcccgcgg tggtcggagt ggatgacggg ttcctgcgac caggccccct 16440 cgatgctgag tggatgcatc gcgccttctc cttcggaccg atgggtgggg tgcggggcgg 16500 gccgggggca cggccgagcc ggtcagctgg agcgtctcca gtaggaaccc tggcgatcga 16560 tctggtggat ctcgtccgtg atgccgtgct cgtcccggaa ctcgtggacg gcctgccggc 16620 acgccggaat gcagtagtcg tcgacgatga cgtacccgcc gtccgacacc ttgtggtaga 16680 ggttggtgag aacctccctg gtggctgcgt acgagtcccc gtcgagcctc agcaccgcga 16740 gcctctcgat gggcgcggtg ggcatcgtgt ccttgaacca gcccgggagg aagcggacct 16800 ggtcgtccag gagtccgtag cgcgcgaagt tccccttcac ggtctccacg tcgaccggga 16860 tgctgaggac gtcgttgtac tggccgaggt cgatgtcgac gtccagctgg tggtcgtcct 16920 cggtggtctt ggggaaaccc tggaaggagt ccgcgaccca caccttccgg tcccgcacgc 16980 cgtgcgcccg gaagacgccg cgggcgaaga tgcaggcccc gccccgccag accccggtct 17040 ccgcgaagtc ccccggcacg ccgtcgcgca gcacgtcctc caggcacttc tgcaggttgt 17100 cgagccgctt gagaccgacc atcgagtgcg ccacgcgcgg aaagtcctca cccaccgagc 17160 gcagttccgc ggaatacgag ctgctggtga tgaggccggc gacattggtc tggtcctcgt 17220 aaatcatgtt cgtcacgacc ttcttcagaa ggtcgagata caggtccgct tcggcagcta 17280 tgacagtcat tttcctcact tacgggtagc agtgcccagc gggcggctcg ttcaggacgg 17340 gggccgccgg ggctgaattc cctgtgtcca cacagatgag gtggatgagg tggatgaggt 17400 agccatctaa ccccagtgat cagattcggg caagggtcga aaacgagcca cgtcttatgt 17460 cgatcctgtc cggaagcgag gggcatatgg tgcagtggcg actgcggccg atctggctga 17520 tccttgctgc ggcgctgacc gtgtgcttgc atgttggacg tagatcacct tctcccgatt 17580 gcattcaggg tgaggaaatc catgaaatct tcaaaagtcg ttcacagccg tcctgcggaa 17640 gcgggcgtcg catggcccgt cgcgcgaacc tgccccttta cgctccctga tcagtacgca 17700 gagaagcgca agaacgagcc catatgccgg gctcaggtct gggacgactc cagaacctgg 17760 ctcatcacca agcacgagca cgtacgagcc cttctcgccg acccccgggt caccgtcgac 17820 ccggccaagc tgcccaggct ctccccctcc gacggcgacg gcggcggctt ccggtccctg 17880 ctgaccatgg accccccgga ccacaacgcc ctccgccgca tgctcatatc cgagttcagc 17940 gtgcaccggg tccgggagat gcgcccgggc atcgagcgca ccgtgcacgg gctgctggac 18000 gggatcctcg aacggcgggg gccggtggac ctggtggccg aactcgcgct gccgatgtcc 18060 accctggtga tctgtcagct cctcggagtg ccctacgaag accgcgagtt cttccaggaa 18120 cgcagcgaac aggccacccg ggtgggcggg agccaggaat cgctgaccgc gctcctggaa 18180 ctacgggact acctggaccg gttggtcacc gcgaagatcg agacgccggg tgacgacctg 18240 ctgtgccggc tcatcgccag tcgactgcac accggtgaga tgcgacacgc cgagatcgtg 18300 gacaacgccg tgctgctgct cgccgccggc cacgagacca gtgccgccat ggtggcactg 18360 ggcatcctga cactgttgcg gcaccccggc gccctggcgg agttgcgggg cgacggtacg 18420 ctgatgccgc agacggtcga cgaactcctg cgtttccact ccatcgcgga cggccttcga 18480 cgggcggtca cggaggacat cgaactcggc ggcatcacgc tgcgcgccgg agacggcctc 18540 atcgtctcgc tggcctccgc caaccgcgac gagagcgcct tcgcctcccc ggacggcttc 18600 gacccgcacc atccggcgag ccggcacgtc gccttcggct acggccccca ccagtgcctg 18660 ggccagaacc tggcccggct ggagctggag gtcaccctgg gcgcggtggt ggagcgcatt 18720 cccacgctca ggctggccgg cgacgccgac gcactgcgcg tcaaacagga ttcgaccatc 18780 ttcgggctgc acgagctgcc ggtcgagtgg tgacggaagg aggacacagc gtgcgggtga 18840 cagtcgacca gagccggtgc ctgggagccg gccagtgcga gcagctggcg ccggaggtct 18900 tccgccagga cgaggaagga ctgagccggg tcctcgtccc cgagcccgat ccggcgtcat 18960 ggccgcgggt gctccagacg gtggacctct gccccgtaca ggccgtcctc atcgacgagg 19020 gccccggtcc cgcgccgcag gacaccaagt gaccgctgac cgctgggccg gccgcacggt 19080 gctcgtcacg ggagcactcg ggttcatcgg ctcccacttc gtccgacagc tggaggcgcg 19140 cggagccgag gtgctcgccc tctaccgcac cgaacggccg caattacagg ccgagttggc 19200 cgcgctcgac cgagtacgcc tgatcaggac ggagctgcgg gacgagtcgg acgtgcgagg 19260 ggccttcaag tacctggcac cctccatcga caccgtcgtc cactgcgcgg ccatggacgg 19320 caacgcgcag ttcaagctgg agcgctcggc cgagatcctc gacagcaacc agcggaccat 19380 ctcccacctg ctgaactgcg tacgggactt cggcgtcggc gaggccgtgg tcatgagctc 19440 ctccgagctg tactgcgcgc cgcccaccgc ggcggcccac gaggacgacg acttccgccg 19500 atccatgcgg tacacggaca acggctacgt cctgtccaag acctacggcg agatcctggc 19560 caggctccac cgcgagcagt tcggcaccaa cgtcttcctg gtgcgaccgg gcaacgtcta 19620 cgggccggga gacggctacg acccctcccg gggccgggtg atccccagca tgctggccaa 19680 ggccgacgcc ggcgaggaga tagagatctg gggggacggc agtcagaccc ggtccttcat 19740 ccacgtcacc gacctggtac gggcctcact gcgcctgctg gagaccggca agtaccccga 19800 gatgaacgtg gccggcgcgg aacaggtctc catcctggag ctcgcccgga tggtgatggc 19860 cgtcctggga cggcccgagc gcatccgcct cgaccccggc cgccccgtcg gcgccccgag 19920 cagacttctg gatctgacca ggatgtcgga agtgatcgac ttcgagcccc agcccctgcg 19980 gaccgggctg gaagagaccg ctcgctggtt ccgccaccac acgcgctgaa cctcctctca 20040 tacccccctg gaaggtaact cgtggtcaca cacgccccga actcgctgat cagtgacata 20100 atccgcgcct ccggcgggca tgacgccgac ctcaaggacc tggccgcccg acacgatccg 20160 gccgacatcg tccgcgtact cctggacgag atcacctcac gctgccccgc tcccgtgaac 20220 gacgtccccg tcctcgtcga gctggccgtc cgggcgggag accgcctctt ccccacctat 20280 ctgtacgtcc tcaagggcgg cccggtgcgc ctcgcggcca aggacgaggc gttcgtcgcc 20340 atgcgcgtcg agtacgagct gggcgaactg gcccgcgagc tgttcggacc ggtgcgggag 20400 aacgtcaccg gcgtccgcgg aacgactctc ttcccctacg tcggggacac ggcgtcggaa 20460 ggcgaggagg actcgggtgc cgagcacatc ggcacgcact tcctggccgc gcagcagggc 20520 tcccagaccg tgctcgccgg ctgccattcc cacaagccgg acctcagcga gctctcctcg 20580 cgctacctca ccccgaagtg gggctcgctg cactggttca ccccccacta cgaccgccac 20640 ttcaggagct accgggacca gcccgtacgc gttctggaga tcggcatcgg cggctacaag 20700 caccccgagt ggggcggcgg ctccctgcgc atgtggaagc acttcttcca tcgcggcgag 20760 atctacggcc tggacatcgt cgacaagtcg cacttcgacg cgccgcgcat cacgaccctg 20820 cgcggcgacc agagcgaccc cgaccacctg cggtcgatcg ccgagaagta cggaccgttc 20880 gacatcgtca tcgacgacgg aagccacatc aacgaccaca tccggacctc gttccaggca 20940 ctgttcccgc atgtgcggcc cggcggcctc tacgtgatcg aggacctgtg gaccgcctac 21000 tggtccggct tcggcggcga cgaggacccg aagcggtaca gcgggacgag cctgggcctg 21060 ctcaagtccc tcgtcgactc gatccagcac gaggaactgc cggaggccgg cgaccaccgt 21120 cccagttacg cggaccagca cgtggtcggc atgcacctct accacaacct ggcgttcatc 21180 gagaagggca ccaacgccga gggcggcatc cccccgtgga tcccacgcga cttcgagacc 21240 ctcgtcgccg tctcctccgg gggccacgca tgaggagccg tcggcaccag ccacccgaac 21300 acacccgacc ggaccgcagg aggcccgcat gcgcgtgacc ctgctgagcg tcggatcccg 21360 aggcgacgtc cagccgttcg tcgccctcgg catcggcctc aaggcccgcg gccacgacgt 21420 caccctggcc gcccccgcca cgctgcggcc actggtcgag cgcgcgggac tgacgtacag 21480 gctgtccccc ggggatcccg acggattctt caccatgccc gaggtcgtcg aagcgctgcg 21540 gcgcggcccc tcgttcaaga acatgctcgc ggggatgccc gaggcgcccg agagctacac 21600 acagcaggtc gtcgacgcga tccacgacgc cgccgagggc gccgacctca tagtgaacgc 21660 gcccctcacc ctggccgccg cgtacgggca cccgcccgcc ccgtgggcct cggtgtcctg 21720 gtggcccaac agcatgacct cggccttccc ggccgtcgaa tccgggcagc gccacctcgg 21780 accgctgacg tccctgtaca accgctacac ccatcgcagg gcggcacgcg acgagtggga 21840 gtggcgacgc cccgagatcg acggctaccg ccgacgcctc ggcctccggc ccttcggcga 21900 cgagtccccg ttcctccgac tggggcacga ccgcccgtac ctgttcccct tcagccccag 21960 cgtgctgccc aagccgcggg actggccgcg ccagagccac gtcaccggct actggttctg 22020 ggaccagcac ggggagccgc ccgccgagct ggagtcgttc ctggaggacg gggagccccc 22080 ggtggcgctc accttcggca gcacctggtc actccaccgg caggaggagg ccctccaggc 22140 cgccctcgac gccgtccgtg gcgtcggacg ccgactggtc atggtcgacg gaccggacag 22200 cgacctgccc gacgacgtgc tccgcctgca ccaggtggac tacgccaccc tcttccccag 22260 gatggccgcg gtgatccacc acggcggcgc cggcacgacc gccgaggtcc tccgggccgg 22320 agtgccccag gtcatcgtgc cggtcttcgc cgatcacccc ttctgggcgg ctcgactgtc 22380 cagaacaggc gtcgccgccc ggccggtccc cttcgcccgc ttcagccgag aggcactggc 22440 gcagagcgtc cgccaggcgg tcaccgatcc cgcgatggcg ggccgggcca ggcgactggg 22500 cgaacgggtc tccaaggaac ggggagtgga caccgcctgc gacatcctcg agaagtgggc 22560 ggagacggca cgcgccacgg cctgacacgg ccaccggcgg gcgggcccgg aagccgcacg 22620 cccgccggcc gacgggtccc gggaccgcgc cgctacgccg acaaccggta ggcggagagc 22680 cgcacggaga gcgtgacccg agtcggcgcc ggcagccgct ggatcgtctc cagatcccgc 22740 tgcgcgtcac ggtgccaggc attgggcccc atgccgacca ggtgcgccag agcctggtgg 22800 tcgagagcca tggtccgggt caactcctcc gtggcgacgg ccgagaagtg cggagcgagc 22860 tgctccgcga gacgcgactc cttgccttcg tccacctgca gcaggccgag ggcgccgatc 22920 acctcccgca ggtgatcggg cagaggagtg acaaccagga gaacgccacg gggatggaga 22980 acgcgatgca gttcaggacc gttgcgggga gcgaacgtgt tgatcaccat gccggctgcg 23040 gcatcccgca gcggaagcgt ctgccaggcg tcggtcaccg cggccgcgat ccgcggatgc 23100 gccttcgcgg cacgccgcac ggcgtacttg gagatgtcca gcagcaggcc ctgggcatcg 23160 gggaacgctt ccatgacccc ggcgtgatag tggcccgtcc ccccaccgat gtcgaccaca 23220 cagccgggca cggccggatc ggccgtccgc cgcgccagat cgaccagcgc atccatcacg 23280 gggtcgtagt gacccgccga caggaatgcg tcccgggcct ccaccatttc cttggtgtcg 23340 gcccgcagct tcgtcgccct gggaagcaga ttcacataac cctgcttcgc gatgtcgaag 23400 gagtgtccgg cggggcagaa aagtgcgcgg tcgccctgag ccagcgaagc accgcagtgc 23460 gggcaggcga ggtagcgcac gatcctgttg agcatggggc accgttcctt cgggcgagtc 23520 ggcagaccgg ccaaccctaa cgcaggcgcc cggccgccca ccgcccggcg cagggccgac 23580 gaaccaccgt gacgtgcacc agccgcgcgt gagaactcct catgcgcgca ccctacggaa 23640 atcggcaggt caaccggcga ttcctgcggg aattccgagc gaaacggcct cactgtgttt 23700 ccccgctgca tttcctcgct gaattcagcg aatcccggca gacgaccggc tctgccggcg 23760 tgacagcccc tatcgatcga ccaggagttt cgatggcccc gaagagtggt gcgcagcgtt 23820 cgagcgacat agccgtcgtc ggcatgtcct gccgccttcc gggggcaccg ggcatcgatg 23880 agttctggca tctgctgacc accggaggca gcgcgatcga gcgtcgcgcc gacggcacct 23940 ggcgcggctc cctggacgga gccgccgact tcgacgccgc cttcttcgac atgacccccc 24000 gccaggccgc cgccgccgac ccgcagcaac gactcatgct ggaactcggc tggacggccc 24060 tggagaacgc cgggatcgtc cccggcagcc tcgccggcac ggacaccggc gtcttcgtcg 24120 gcatcgcggc cgacgactac gcggcactcc tgcaccggtc cgccaccccc gtcagcgggc 24180 acaccgcgac gggcctgagc cggggcatgg ccgccaaccg cctctcctac ctcctgggcc 24240 tgcgcggtcc cagcctcgcg gtggacagcg cgcagtcctc ctcgctcgtc gcggtccacc 24300 tggcctgcga gagcctgcgc cgcggcgagt ccgacctcgc gatcgtcggc ggcgtcagcc 24360 tgatcctcgc cgaggacagc acggcgggca tggagctcat gggcgcgctc tcgccggacg 24420 gccgctgcca caccttcgac gcacgcgcca acggctacgt acgcggtgag ggcggagcct 24480 gcgtcgtcct caagcccctg gagcgggcac tggccgacgg ggaccgcgtc cactgcgtcg 24540 tccgaggaag cgcggtcaac aacgacggcg gcggctccac cctgaccacc ccccaccgcg 24600 aggcccaggc cgccgtcctg cgggcggcgt acgaacgggc cggggtcggc ccggaccagg 24660 tgtcctacgt cgaactgcac ggtacgggga cgccggtcgg cgaccccgtc gaggcggcgg 24720 ctctcggcgc ggtcctcggc acggcccacg gccgtaacgc cccgctgtcc gtgggatcgg 24780 tcaagacgaa cgtcggccac ctggaggcgg ccgcgggcct cgtgggattc gtgaaggcag 24840 ccctgtgcgt ccgcgagggc gtggtgccgc cgagcctgaa ccacgcgacg cccaaccctg 24900 ccatccccat ggaccggcta aacctgcgcg tacccacgcg actggagccc tggccgcacc 24960 cggacgaccg agcgaccggc cggctgcgac tggccggcgt ctcgtccttc ggcatgggtg 25020 ggacgaacgc gcatgtggtg gtggaggagg cgccgcttcc ggaggccggg gagccggtcg 25080 gggccggtgt gcctttggct gtggtgccgg tggtggtgtc gggtcgttct gcgggtgcgg 25140 tggctgaact ggcctcccgc ttgaacgagt cggttcgttc ggatcggttg gtggatgtgg 25200 ggttgtcgtc ggtggtgtcg cggtcggtgt tcgagcatcg gtccgtggtt ctggcggggg 25260 actctgccga gctgagtgcc ggtttggatg ctctggccgc tgacggagtg tctcctgtcc 25320 tggtgtcggg tgtggcgtcg gtcgggggtg gccggtcggt gttcgtgttc ccgggtgcgg 25380 gggtgaagtg ggcggggatg gcgctcgggt tgtgggcgga gtctgctgtg tttgcggagt 25440 cgatggcgcg gtgtgaggcg gcgttcgccg ggttggtgga gtggcgtctg gcggatgtgc 25500 tgggtgatgg ggctgcgttg gagcgtgagg acgtggtgca gccggcgtcg ttcgcggtga 25560 tggtgtcgtt ggcggcgttg tggcggtcgt tgggtgtggt gccggatgcg gtggtggggc 25620 attcgcaggg ggagatcgct gctgcggtgg tggcgggtgg tctgtcgttg gaggacgggg 25680 cgcgtgtggt ggtgttgcgt gcgcgggtgg ctgaggaggt tttgtcgggt ggggggattg 25740 cttcggtgcg tctttcgcgg gccgaggtgg aggagcggtt ggcgggtggg ggtggtgggt 25800 tgagtgtggc ggtggtgaat gcgccgtcgt cgacggtggt ggcgggtgag ttgggggatt 25860 tggatcggtt tgttgcggcg tgtgaggcgg agggggtgcg ggcgcgtcgg ctggagttcg 25920 ggtatgcgtc gcattcgagg ttcgtggagc cggtgcgtga gcggttgttg gaggggttgg 25980 ccgatgtccg tccggtgagg gggcggattc cgttctattc gacggtggag gctgcggagt 26040 tcgatacggc tggtctggat gcggagtact ggttcgggaa tctgcgtcgg ccggttcgct 26100 tccaggagac ggtcgagcgg ctgttggcgg atggtttccg ggtgttcgtg gagtgcggcg 26160 cgcatccggt gctgaccggg gcggtgcagg agaccgcgga gactgcgggc cgggagatct 26220 gctccgtcgg atccctgcgt cgtgacgagg gtggactgcg tcgcttcctg acctctgcgg 26280 cggaggcgtt cgtccagggg gtggaggtgt cctggccggt gctgttcgac ggcaccggcg 26340 cccggacggt cgacctgccc acctacccct tccaacgccg gcaccactgg gcacccgacg 26400 gctccgcgtc ggcggcgccc acacgggaca tccgaccgga cgagaccgcc gcggttccag 26460 cggacacgat ggacctcgcg ggacaacttc gcgcggacgt ggcgtcgttg cccaccaccg 26520 agcagatcgc gcggttgctc gaccaggtac gcgacggtgt cgccacggtc ctcggactgg 26580 acgcccggga cgaggtgcgc gcggaggcga cgttcaagga actgggcgtc gaatcgctga 26640 ccggcgtcga gctgaagaac cacctccgtg cccggaccgg actgcacgtc cccacctcgc 26700 tgatctacga ctgcccgact cccctcgccg ccgctcacta cctccgcgac gagctcttgg 26760 gccgacccgc ggagcaggcc gtcgtccccg ccggcatccc ggtcgacgaa ccgatcgcga 26820 tcgtggggat ggggtgccgt ctgccgggtg gggtgtcgtc gccggagggg ttgtgggatc 26880 tggtggcgtc gggggtggat gcggtttctc cgttccccac ggatcggggt tgggatgtgg 26940 ggggtctgtt cgatccggag ccgggggtgc cggggcgttc gtatgtgcgt gagggcgggt 27000 tccttcatga ggcgggggag ttcgacgcgg ggttcttcgg tatctctccg cgtgaggcgt 27060 tggcgatgga tccgcagcag cggttgttgc tggagacgtc gtgggaggcg ttggagcggg 27120 cgggcatcga tccgcacacg cttcgcggtt cacggaccgg cgtctacgcc ggagtgatgg 27180 cccaggaata cggcccccga ctccacgaag gcgcagacgg atacgagggc tatctgctga 27240 ccggatcctc cagcagtgtc gcctcgggtc gtatctcgta cgtgctgggt ctggaagggc 27300 cggcggtgac ggtggacacc gcgtgctcgt cgtcgctggt cgcgctgcac ctggccgtgc 27360 gggcgctgcg cagcggtgag tgcgacctcg ccctcgccgg cggcgcgacc gtcatggccg 27420 aacccggcat gttcgtggag ttctcacggc agcgcgggct gtctgcccac ggacggtgca 27480 aggcgtactc ggactcggcc gatggcacgg gctgggccga gggggcgggt gtgctgctcg 27540 tcgagcggtt gtcggatgcg gtacgtcatg ggcgtcgggt gctggcggtc gtgcgtggtt 27600 ccgcggtcaa ccaggacggt gcgagcaacg gactgacggc gccgaacggg cggtcccagt 27660 cgcgtttgat ccgtcaggcg ttggcggatg cgcggttggg tgtggctgat gtggatgtgg 27720 tggagggcca cggcacgggg acgcgtctgg gtgatccgat cgaggcgcag gcgttgttgg 27780 cgacgtatgg gcagcgggat gcgggtcggc ctctgcggct tggttcgctg aagtcgaacg 27840 tggggcatac gcaggcggct gccggtgtgg cgggcgtgat caagatggtc atggcgatgc 27900 ggcacggtgt cctgccgaag acgctgcacg tggatgagcc gacggcggag gtggactggt 27960 cggccggcgc ggtgtccctg ctgagggagc aggaggcgtg gccgcgtggc gagcgtgtgc 28020 ggcgggccgg agtctcctcg ttcggcgtga gtgggacgaa cgcgcatgtg gtggtcgagg 28080 aggcgccggt tccggaggac ggggaggcga tcgagggcgg tgcgcctttg gctgtggtgc 28140 cggtggtggt gtcgggtcgt tctgcgggtg cggtggcgga gctggcgggc cgggtcagcg 28200 aggtcgctgg gtctggtcgg ttggtggatg tggggttgtc gtcggtggtg tcgcggtcgg 28260 tgttcgagca ccggtccgtg gtgctggcgg gggactctgc cgagctgaat gccggtctgg 28320 atgctctggc cgctgacgga gtgtctcctg tcctggtgtc gggtgtggcg tcgggtgagg 28380 gtggccggtc ggtgttcgtg ttccctggtc aggggacgca gtgggcgggg atggcgctcg 28440 ggttgtgggc ggagtcggcg gtgttcgcgg agtcgatggc gcggtgtgag gcggcgttcg 28500 ccgggttggt ggagtggcgt ctggcggatg tgctgggtga cgggtctgcg ttggagcggg 28560 tcgatgtggt gcagccggcg tcgttcgcgg tgatggtgtc gctggcggag ttgtggcggt 28620 cgttgggtgt ggtgccggat gcggtggtgg ggcattcgca gggggagatc gctgctgcgg 28680 tggtggcggg tggtctctcg ctggaggatg gcgcgcgtgt ggtggtgttg cgtgcgcggt 28740 tgataggccg tgagctggcc gggcgcggtg ggatggcgtc ggtggcgctg ccggtcgcgg 28800 tggtggagga gcgtctggcg gggtgggcgg ggcgtctggg tgtggcggtg gtcaacggac 28860 cctccgccac ggtcgtcgcg ggtgatgtgg atgcggtggg ggagtttgtg accgcgtgcg 28920 aggtggaggg ggttcgggcg cgtgttctgc cggtggacta cgcctcgcac tcggcgcacg 28980 tggaggacct gaaagccgag cttgaacaga ttctggccgg catcggcccg gtgaccggtg 29040 gcatcccgtt ctattcgacg tccgaagccg cgcagatcga cacggctggt ctggacgcgg 29100 ggtactggtt cgggaatctg cgtcggccgg tgcggttcca ggagacggtc gagcggttgc 29160 tggcggatgg tttccgggtg ttcgtggagt gtggcgcgca tccggtgctg acgggggcgg 29220 tgcaggagac cgcggaatcc accggtcgcc aggtgtgtgc ggtcggatcc ctgcgtcgtg 29280 acgagggagg tctgcgccgc ttcctgacct ctgcggcgga ggcgttcgtc cagggggtcg 29340 gggtgtcctg gccggcactg ttcgacggca ccggcgcccg cacggtcgac ctgcccacct 29400 atcccttcca gcgtcggcgt tactggctgg agtcacgtcc tcctgcggcg gttgttccgt 29460 cgggggtcca ggacggattg tcgtatgagg tggtgtggaa gagcctgccg gtacgggagt 29520 cgtcgcgtct tgacggccgg tggctgctcg tcgtgcccga aaccctggac gccgacggca 29580 cgcggatcgc ccacgacctc cagcacgccc tcaccaccca cggcgccacg gtctcccgtg 29640 tgtcggtcga cgtgacgacg atcgaccgcg ccgacctgtc ggcgcggctc accacgagcg 29700 cggccgaaga ccaggaaccg cttgggcgag tggtgtccct cctggggtgg gccgagggag 29760 tacgggccca tggcccgaac gtaccgactt ccgtcgccgc ctccctggca ctcgtgcagg 29820 ctgtcggcga tgccgggttc ggtgttccgg tgtgggcggt gacgcggggt gcggtgtccg 29880 tggtgcctgg tgaggtgccg gagacggcgg gtgcgcaact gtgggcgctc ggccgggtcg 29940 ccggtctcga acttcccgac cgttggggtg gtctgatcga tcttccggcg gatgccgatg 30000 cgcgtacggc ggggcttgcg gtgcgggccc tggccgccgg gatcgccgat ggtgaggacc 30060 aggtggcggt gcgcccctcg ggtgcctacg gccggcgtgt agttcaggca gcccaccggg 30120 agccgtcggg agcgaagacg gagtggcgac cgcgtggcac cgtgctcgtc accgggggaa 30180 tgggcgccat cggcactcgg gtggcccgct ggctggcccg gaacggagcc gaacacctgg 30240 tgctgaccgg ccgccgcggt gccgggaccc ccggcgcgga cgagctggcg ggagagctga 30300 gggcgtccgg agtccaggtc acgctcgccg cctgcgacgt gtccgatcgt gccgcgctgg 30360 ccgcgctgct cgacgcgcat ccgccgaccg ccgtcttcca cacggccggt gtactgaacg 30420 acggaacggt cgacacgctc actcccgctc acctggacgg ggtcctgagc cccaaggcga 30480 cggccgccgt tcacctgcac gagctcaccg cccacctgga cctggacgcc ttcgtcctct 30540 tcgcctccgt caccggcgta tggggtaacg gcggccaggc cgggtacgcc atggccaacg 30600 cggctctgga cgcgctcgcc gagcagcgcc gtgccggcgg acttgcggcg acctccatca 30660 gttggggcct ctggggtggc ggcggcatgg ccgagggtga cggcgaggtg agcctcaacc 30720 gtcgtggaat ccgcgctctt gagcccgcca ccggcatcga ggcgctgcag cggacgctcg 30780 accagggcgc cacctgccgc accgtcgtcg acgtggactg gggtcagttc gctcctcgta 30840 cggcggcgct gcggcgcggg cggctcttcg cggatctgcc cgaggtgcgg cgtgtcctgg 30900 agtccgaggg ggttgcacgg gaggacgccg gaaccgtcga gcccggcgcc gtgctcgccg 30960 agcgcctcgc atcgcgctcc gaggccgaac agcgacgcat gctcgtcgag ttggtacgag 31020 ccgaagcggc tgccgtcctg cgtcacgaca cgacggacct cctggcgccg cgcaggtcgt 31080 tcaaggacgc cgggttcgac tccttgaccg cgctggagct ccgtaaccgg ctgaacaccg 31140 ccaccggtgt cgtccttccc gtcaccgtcg tcttcgacca cccgaacccc ggtgcactgg 31200 cggacttcct gtacggcgaa gcactgggcc tgtccgcggc caggtcttcc gcgagcgata 31260 cggccgacac gacccgcccg gccgccgccc ccgaagagcc gatcgcgatc gtcggaatgg 31320 cctgccgcta cccgggcgag gcccgttccc ccgaggaact gtggaagttg ctcatcgacg 31380 aacgggacgt catcggcccc atgcccacgg atcggggttg ggatgtgggg ggtctgttcg 31440 atccggagcc gggggtgccg gggcgttcgt atgtgcgtga gggcgggttc cttcatgagg 31500 cgggggagtt cgacgcgggg ttcttcggta tttctccgcg tgaggcgttg gcgatggatc 31560 cgcagcagcg gttgttgctg gagacgtcgt gggaggcgtt ggagcgggcg ggcatcgatc 31620 cgcacacgct ccgcggctca cagaccggcg tctacgcggg gatgttccac caggagtacg 31680 cgacccggct gcacgaggca cccgtggagt tcgaaggcca cttgctgacg gggacgtccg 31740 ggagtgtggc ttcgggtcgt atctcgtatg tgctgggtct ggaggggccg gcggtgacgg 31800 tggacacggc gtgttcgtcg tcgttggtgg cgctgcatct ggcggtgcgg gcgttgcgga 31860 gtggtgagtg tgaccttgct cttgcgggtg gggtgacggt gatggcggag ccgggtgtgt 31920 tcgtggagtt ctcgcggcag cgggggttgg ctgcggacgg gcggtgcaag gcgttcgcgg 31980 ctgctgccga tggcacgggc tgggccgagg gtgtgggcgt gctggcggtg gagcggttgt 32040 cggatgcggt gcgtcatggg cgtcgggtgc tggcggtggt gcgtggctcg gcggtgaatc 32100 aggacggtgc gagcaatggg ttgacggctc cgaacggtcc gtcgcagcag cgggtgattc 32160 gtcaggcgtt ggcggatgcg cggttgggtg tggctgatgt ggatgtggtg gaggggcatg 32220 ggacggggac gcgtctgggt gatccgatcg aggcgcaggc gttgttggcg acgtatgggc 32280 agcgggatgc gggtcggcct ctgcggcttg gttcgctgaa gtcgaatgtg gggcatacgc 32340 aggcggctgc cggtgtggcg ggcgtgatca agatggtcat ggcgatgcgg cacggggtcc 32400 tgccgaagac gctgcacgtc gatgaggtct ctccgcacgt cgactggtcg gcgggcgcgg 32460 tgtccctgct gacggagcag gagccgtggc cccgtggtga gcgcgtacgg cgggctggtg 32520 tctccgcgtt cggtgtgagt gggacgaacg cgcatgtggt ggtggaggag gcacctgctt 32580 cggaggcgcc ggtcgcggtg gagccggtgg agccgggggc tgtggggctt cttccggtgg 32640 tgcccgtggt ggtgtcgggt cgttctgcgg gtgcggtggc tgaactggcc tcccgcttga 32700 acgagtcggt tcgttcggat cggttggtgg atgtggggtt gtcgtcggtg gtgtcgcggt 32760 cggtgttcga gcatcggtcc gtggttctgg cgggggactc tgccgagctg agtgccggtt 32820 tggatgctct ggccgctgac ggagtgtctc ctgtcctggt gtcgggtgtg gcgtcggtcg 32880 ggggtggccg gtcggtgttc gtgttcccgg gtgcgggggt gaagtgggcg gggatggcgc 32940 tcgggttgtg ggcggagtct gctgtgtttg cggagtcgat ggcgcggtgt gaggcggcgt 33000 tcgccgggtt ggtggagtgg cgtctggcgg atgtgctggg tgatggggct gcgttggagc 33060 gtgaggacgt ggtgcagccg gcgtcgttcg cggtgatggt gtcgttggcg gcgttgtggc 33120 ggtcgttggg tgtggtgccg gatgcggtgg tggggcattc gcagggggag atcgctgctg 33180 cggtggtggc gggtggtctg tcgttggagg acggggcgcg tgtggtggtg ttgcgggcgc 33240 gggtggctga ggaggttttg tcgggtgggg ggattgcttc ggtgcgtctt tcgcgggccg 33300 aggtggagga gcggttggcg ggtgggggtg gtgggttgag tgtggcggtg gtgaatgcgc 33360 cgtcgtcgac ggtggtggcg ggtgagttgg gggagttgga tcggtttgtt gcggcgtgtg 33420 aggcggaggg ggtgcgggcg cgtcggctgg agttcgggta tgcgtcgcat tcgaggttcg 33480 tggagccggt gcgtgagcgg ttgttggagg ggttggccga tgtccgtccg gtgagggggc 33540 ggattccgtt ctattcgacg gtggaggctg gggagttcga tacggctggt ctggatgcgg 33600 agtactggtt cgggaatctg cgtcggccgg ttcggttcca ggagacggtc gagcggttgt 33660 tggcggatgg tttccgggtg ttcgtggagt gtggtgcgca tccggtgctg accggggcgg 33720 tgcaggagac cgcggagact gcgggccggg aggtgtgtgc ggttggttcg ctgcgtcgtg 33780 acgagggagg tctccgtcgc ttcctgacct ctgcggcgga ggcgttcgtc cagggggtgg 33840 aggtgtcctg gccggtgctg ttcgacggca ccggcgcccg cacggtcgac ctgcccacct 33900 accccttcca acgccgccac tactgggcac agtcctcgcc cgccggcgcc ggcagctctg 33960 ctgcggcccg cttcggtatg acctgggagg agcatccgct cctcggcggc gcgctgccgc 34020 tcgcggactc cggcgagctg ctgctcgtcg ggaggatctc cccggcctcc cactcctgga 34080 tcgccgacca caccgtggcc gggaccgccc tgctgcccgg gacggccttc gtcgacatgg 34140 cactgcacgc cgccgcggtc gcgggctgtg cgggtgtgga ggagctgagc atcgaggccc 34200 cgctgccggt gcacggcggg atccggctcc aggtggtgat cgacgagccc gactcctccg 34260 cgcggcgccg cgtgagcgtg ttcgcgaggc cggaagagga agacggggac gccggccgct 34320 ggacccgaca cgccaccggc gtgctgaccc ccgacgtcgc ccccgagccg ggccggccgc 34380 agtggtgccg gcaggcctgg ccgccgagcg gctccgtccg ggtggaggcg tcggagctct 34440 acgaccggtt ctccgcgctg ggatacgact acggcgaggt cttcgccggg gtcgaggccg 34500 tctggctgcg cgagggcgag gccttcgccg aggtccgcct gcccacgggc gcggcgcccg 34560 acgccgagcg gttcggggtg caccccggcc tcctcgacgc ggctctgcac ccctggctgc 34620 tgggcgactt cctgtcgcgg cccgacggcg gatccgtact gctgccgttc gcgtggcgcg 34680 gcatcacgct ccacacggcc ggtgccgacg cgctgcgggt ccgtctcgga ccggccggag 34740 aaggcgctct gtcgctcgaa gccgtcgacc tctccggtgc cccggtgctg tcgatggacg 34800 cactggtgct gcgtccgctc gcccaggacc gcctggcgga actggtcggc ggcacgacct 34860 ccaccccgct gtaccgcgtg gactggcagc ggagcccgat cgcgaggacg gcgccgtcgg 34920 ccacggggct cttcggctcc ctcccgtccg gtgccgtccg ccgctgggcg gtcgtcgggc 34980 agggcggtgt cgccgcacgg tacgcgacgg cggaacccgg cacggggtgc gtcggggtct 35040 tccccgacct ggacgcactg cgtacgacgc tggactccgg agcggacggc cccgacatcg 35100 tcctcgccga cttcggggcc cggccaggcg acgccgcgcc gcacgggacg gatccggccg 35160 acggcgcacg cgacacggtc cggcgggggc tcgccctcat acagggctgg ctgtccgacg 35220 agcgcttcgc cgccgcgcgt ctcgccgtgc tcaccgagca cgccgtcgcc accgaggcgg 35280 acacccgccg gacggacctc gcgggctcgg cactgtgggg gctgatgcgt tcggcgcaga 35340 ccgagcaccc cgaccgcttc gtcctcgtcg accacgacgg gcaggacgcc tcgtaccgga 35400 cgctgcccac cgcgctcgac agcgaaatcc cgcaactggc gctccgagcc ggggagacgc 35460 tggcccccga actggcggtc ctgccgagtc cggccgacgg ggggcccgcg acaagcgcgg 35520 cgttcgatcc cgaaggcacg gtactcgtca ccggagccac cggcaccctc ggcagcctgc 35580 tggcccggca cctggtcacg gcacacggcg tacggcatct gctgctgctc agccgcagcg 35640 gacgcgaagc cgcgggggcc gccgaactgg agcgtgaact ccgtcaacgg ggagccgagt 35700 tccagctcct ctcctgtgac gcgacggacc gggcagcgct gaaggaggcc ctcgccaccg 35760 tccccgccgc ccacccgctg accgcggtga tccacacggc cggcgtcctc gacgacggcg 35820 tcgtcgaggc gctgaccccc gaacggctgg accgcgtgct gcgccccaag gcggacgccg 35880 cgctgaacct gcacgacctg accgagggaa tgccgctgaa ggcgttcgtc ctgtactccg 35940 gggcggtcgg actgctgggt ggagcgggcc aggccaacta cgcggcagcc aacgcgttcc 36000 tggacggcct ggcccaacac cggcacgcgc aagggctgcc cgcggtgtcc ctggcatggg 36060 gactctggag cgccaccagc acgttcaccg accatctcgg cgaggtggac ctgcggcgca 36120 tggagcggtc cggcatcacg ccgctcacgg acgagcaggg ccttgacctg ttcgaccggg 36180 ccctcggcgc cgcggtggac gcgccgcagc tctgcgtgat ggggctggac acggcggcgc 36240 tgcgccggca ggcggccgag cacgggccga cttcgatgcc tcctctgctg cgtacgctgg 36300 cggcgcctcc cgtacggcgc ggcgcggggc gctccggccg gggcggacgg gcggcgtccg 36360 ccacggacgc gccgagccgg gcgcaggccc tgcgcgagcg actgacgggc ctggacgcgg 36420 cggcacggcg ggacgaactc ctggtcctgt cgcaggcgca gttggccgat gtgctgggct 36480 tcgccgacaa gaccgcggtg gaccccgttc gttccttccg cgagatcggt ctggactcgc 36540 tgaccgccgt cgagctgcgc aaccggctcg gtgtcgtcac cggactgcgg ctgccgccgg 36600 cgctggtctt cgaccacccc aacctcgacg cgctcgcggc ccacctggcg gagctcctcg 36660 cggctgaggg ccgggacgac gcgggcgccg cggcgctctc gggaatcgac gccctggacc 36720 gggcggtccg ggagatggcg gccgacgaca cgcgccgtga cgccgtccgc cgacgcctcg 36780 cggaactgct ggcggtggtc ggcgacgccc cgcgggacgg cggccgcgcc ccacgggcgg 36840 ccgccgacgc gggaggccgc gacgctcaag cggaccccga cctgctgggc cggctggact 36900 ccgcctccga cgacgatctg ttcgcgttca tcgaagacca gctgtgagcg ggacgccgcg 36960 cgcgttcccc acccgtccct aagcgccgca tcaggcgcac tcgcaccgac acgagcacgc 37020 aggccaggag ggtccggtcg atgacggcca acgatgacaa gatccgcgac tacctgaagc 37080 gggtcgtcgc cgagctgcac agcacgcggc aacggctcaa cgccttggag cacgacgccc 37140 gcgagcccat cgccatcgtg gggatgagct gccggctgcc cggcggggtg accacccccg 37200 agagcctgtg gaggctggtc gactccggca ccgacgccgc ctcgccgttc cccgacgacc 37260 ggggctggga cctggacgcg ctccaccatc cggagtcggg agccgtccac tcccgcgagg 37320 gcggattcct ccacgacagc gcggacttcg acgcggagtt cttcggcatc agcccgcgag 37380 aggccctggc catggacccg cagcagcggc tgctgctgga gaccgcctgg gaggtgttcg 37440 agcgcgccgg catcgacccg gtctccgccc gcggctcccg cacgggggtg tacgcgggcg 37500 tcatgtacca cgactacggc gcccggctga acgagatccc gccgggcctc gagggctacc 37560 tggtcaacgg cagcgcgggc agcatcgcct cgggccgggt ggcctacacc ctcggtctgg 37620 agggccccgc cgtcaccgtc gacacggcct gctcctcgtc actggtcgcc gtgcacctgg 37680 cggcacaggc actgcggcgg cgggagtgcg acatggcgct cgcgggcggc gcgaccgtcc 37740 tgtccacccc cgacctgttc atcgacttcg cgcgactcgg cggcctggcc tccgacgggc 37800 gctgcaaggc gttctccgac gccgccgacg gcaccagctt cgccgagggc gccggcctgc 37860 tgctcctcat gcggctgtcg gacgcggtgg ccgagggcca caccgtcctg gcggtcgtcc 37920 gaggctccgc cgtcaaccag gacggggcga gcaacggcct gacggccccc aacggcctcg 37980 cccagcaacg cgtgatccgc gaggcgctcg ccgacgcgga cctggacccc gaccagatcg 38040 acgcggtgga ggcgcacggc accggaacca ggctcggcga ccccatcgag gcgcaggccc 38100 tgctgcacac gtacggcacg agccgcagcc ccgaacgacc cctgtggctc ggttcgctga 38160 agtccaacat cggccacacc caggccgccg ccggagtggc cggagtcatc aagacggtgc 38220 tggcgatgcg ccacggacgg ctgccccgca cactgcacgt cacccgcccc tccagccggg 38280 tggaatggtc ggcgggcgcg gtggaactgc tcacgcgggc acaggactgg cccggccagg 38340 ggaacgcccc gcgccgcgcc ggagtgtcgt ccttcggtgc cagcggcacc aacgcacacc 38400 tgatcctgga aggcgtcccg gacggcgaca tcacggtcgc ggagacccga ccggccaccg 38460 gcggcggcgc ctggccgctc gcgggccgga ccgaagcggc cctgcgcgca caggcccggc 38520 ggctccacga ccacctcgcc gcccgccccc acgtctcacc cgccgcggtc gggcggacgc 38580 tggtccgctc ccgcacggcg ttcgagcacc gggccgtcgt cctcggacag gacaccgccg 38640 acctcctgag cggcctcgcg gagctggcgt ccggcggcgc tcacggaccc ggcgtgatca 38700 ccggccgggc cgcgcgcggc cgccgtaccg cactgctctt caccggacag ggcagccagc 38760 ggccgggtgc cggacggcat ctctacgagc ggtacgaggt gttcgcccgc gccctggacg 38820 agacggccgc ggcactcgac cggcacctcg accgcccgct gcgcgacgtg atgttcgcgg 38880 agccgggcgg cgcgacggcc ggactcctcg accgcaccga gtacacccag cccgcactgt 38940 tcgccctgga agtcgccctc ttccgactgg tgaccgccgg gggcctgcgc cccgacgcac 39000 tcctcgggca ctccgtcggc gaactggccg ccgcccacgt cgccggagtg ttcaccctgc 39060 ccgacgccgc ccgcctggtg acggcgcgag gccgactgat gggcgagctg ccggccggtg 39120 gcgccatgat ggcgatccag gcgagcggcc cggagatcga ggagacgatc acggcgctcg 39180 cggcccaccg gtcggcgcgc gtcgccgtcg ccgcactcaa cggtcccgac gccaccgtga 39240 tctcgggcga cgaggacgtg gtcgccgaac tcgccacgct gtggcgggag cggggccgcc 39300 gcaccagggc gctgcccgtc agccacgcct tccactcgcc gcacatggac gccgcactgg 39360 aaccgttcgc ccggatcgcg cgcgacgtct cctacgccga accgcgcatc ccggtggtct 39420 ccaacctgac cggcggcatc gcgtcggcca cgacgctgtg cgcccccgag tactgggtgc 39480 gccacgcgcg cgaggccgtg cgcttcagcg acggcttccg cgccctgcgc gaccagggga 39540 tcgacacctt catcgagctc ggaccggacg gcgtgctgtc cgccctgggc cgcgactgcc 39600 tccgcgagga ggaaggagac gccccacgcc aggacggctc ggcggacccc gacacgaccg 39660 gctcccgcgc cgacgggggg cggcgacccg tgctgacggt gccgctgctg cgccgggacc 39720 gcgacgagac gaccacctgc ctcggggccc tggccaccgt ccacacccac ggcgtccccg 39780 tcgacctcgc ggccgtgcac ggcgcccccg aggggcccgc cgtcgagctc cccacctacg 39840 ccttccaacg cacgcgctac tggctggacg ccccggcccc cgccgccggc cccaccgcca 39900 ccggtctgga ggcgacggac cagcccctgc tcccggccgt catcgacctg cccgacgggg 39960 aaggcaccgt acggaccgga ctgctctccc tgcgcaccca tccgtggatc gccgaccacc 40020 gcgtccgcga ccacgccgtg gtgcccggag cggccctgct ggacgtcgcc gcctgggcgg 40080 gcaccgaagc gggctgcccc cgggtcgccg aactgacctt cgccacgccc ctcgtcctgc 40140 ccgagaacgg agaaggagtc cgactgcgcg tgacggtcag cggccccgac gcggaaggca 40200 tccgttcgct acgcatcgac tcccggcccg ccgacacggt ccgtaccgcc gatgccccct 40260 ccgactggac ccgccacgcg tccggcaccc tcgtccccgc acccgaggag gccggcgacg 40320 gcaccggcgt gccgaccgaa ctgctcggcg cctggccccc ggccgacgcg accccggtcg 40380 ccctcgacgc ggacgccgtc gcggccgagt atcagcgcct cgcggccggc ggcgtgacgt 40440 acggccccgc gttccgggca ctgcgcgccg tctggcgccg cggcgcagag gtcttcgccg 40500 aggtccggct tcccggccag gcggccgccg acgcctcgcg gtacggcatg cacccggccc 40560 tgctggacgc cctgacgcac gccaccgggt tcggcgagcg gtccaccgag gcccgcggcc 40620 tggtcccgtt cgcctggagt gacgtccgga tccacgtccg cggcgccgac tccctgcgcg 40680 tacgcatcgc gccggccggc cccgacgccg tgaccgtcgc cgcggtcgac ccgacgggcc 40740 gcccggtcct cgccgcccgc tcgctcacgc tgcgccccct ggcggagagc cggttccagg 40800 acccggaggc ggacagcacg ccgctgtacc gactggagtg gacaccggcc cccggttccg 40860 tgaccgggca cgccggtcca aggcaggcgg cagcggagtg gggcgtcctc ggcgacccgg 40920 tccaggccct cctcgacgcc gtgcgcgacg gggcggaggc acccgtgcga acccatgacg 40980 acctgctcgc gctcgcggcc tccgacacgg ccccgcccga ccatgtgctg gcgctgctgg 41040 gccacgacgg ggacgctctc gccacgggcg cccacgacct ggccgcacgc gccctggccc 41100 tggtacaggg ctggctgacc cacgcccgct tcgccgacgc gcgactggtc gtgctgacgc 41160 agggggcggt gacggccggc acgagccccg tccacccggc cgcggccgcc gcctgggggc 41220 tgctgcgcag cgcacagtcc gagcacccgg gccgcttcgt cctcgtcgac gcggaccccg 41280 ccgacccggc cgcctcgtac cgttccctgc cacgggccgt cgcctccggg gcgtcccaac 41340 tcgccctgcg cggcgccgag atcctcgtcc cccggctcgc ccggggaacg gaccgacagg 41400 ccaccgtgcc cggacacccc ggcgacgtca ccgcaccgga gacgaccgct gcccccgagc 41460 cggccccgtc cggcaccccc tccggcccct ggcccgcgga cggcaccgtg ctcgtcacgg 41520 gcggaaccgg gaccctgggc aaggccgtgg cccggcacct cgtgaccaag cacggtgtcc 41580 ggcacctgat cctggccggt cggcgaggcg cggacacccc cggggcggcc gacctggcca 41640 ccgaactgac cggcctgggc gccaccgtga acatcgtccg ctgcgatgcc gccgaccgct 41700 cggcgctcga aggcgtcctg gccgccgtcc ccgccgcgca cccgctcacc gccgtcgtgc 41760 acaccgccgg agtgctcgac gacggcatcg tcacggcgca gacgccccga cgcctctcgg 41820 cggtcctgcg cgccaaggcg gacgcggtca gccacctgca cgaactgacc cgcgacctgg 41880 acctgtccgc cttcgtcctc ttctcatcgg ccgccggaac cctcggcagc cccggccagt 41940 ccggctacgc ggccgccaac agcttcctcg acgcgttcgc cgcctggcgg cgagcgcagg 42000 gcctccccgc cgtgtccctg gcatggggac tgtggggtga cggcggtgac ggtcgtgacg 42060 gcggtggctc ggcggccgac ggcatgggag cgagcctggc cgccgccgac ctggcacggc 42120 tgcgccgttc cggcatcctc ccgctcgacc cggccgaagc gctgcgcctg ttcgacgagg 42180 cctgcgaccc cgccaggacc gaggccgtac tgctgccgat ccgcctcgac ctgaccggcc 42240 tgcgcgcccg ttccgcccgc ggcgccgtac acgcgagcgt ggtgcccgaa gtgctgcaca 42300 ccttggtgcc cccgcccgcc ggtgccggat ccccggccgg tgccgacgcg tcggatcccg 42360 cggcgggcca ggcgcccccg gccccggcgt ccgacaccct ggccgaacgg ctcgccggga 42420 agccccgagg cgaacggctc accgccctca ccgaactggt acgcaccgag atcgcctcgg 42480 tactcgggca ccccgactcc ggccgcgtcc agctccagtc ctccttcaag gagtccggct 42540 tcgactcgct caccgccgtc gaactccgca accggctcac cgcggccacc ggaacgaagc 42600 ttcccgccac cctcgtcttc gaccatccga cacccgcggc actcgtcgac cacctggaac 42660 aggaactgcc gaaggcagca caggagatcc cggcggacct cccggccgtt ctcgacgcac 42720 tcgaccggat ccgggacgga ctcgccaccg ccgccaccga cgacagcagc cgcgaccaca 42780 tcgcggagcg tctccaggcg ttgctcggca cgctcacctc ggctgcgggc gtcagccgcc 42840 cgaccggcag cccgggcgag cacgaccggc agggccccga tgagctgtcg ctcggccaac 42900 gactcgccgc cagcagcgac gacgaactct tcgacctctt cgacagcgac ttccgatcga 42960 cgtagcccag ggccaccctt ccgcctccgc cgcccgcccc acacccctgg agaacagcac 43020 gatgtcttcc acatcgcccg ccaccaacga agagaagctc cgcgactacc tccgccgcgc 43080 catgaccgac ctgcacgagg cccgcgagca gatccgccgg accgagtcgg ccaggcacga 43140 gccgatcgcg atcgtgggga tggggtgccg tctgccgggt ggggtgtcgt cgccggaggg 43200 gttgtgggat ctggtggcgt cgggggtgga tgcggtttct ccgttcccca cggatcgggg 43260 ttgggatgtg gggggtctgt tcgatccgga gccgggggtg ccggggcgtt cgtatgtgcg 43320 tgagggcggg ttccttcatg aggcggggga gttcgacgcg gggttcttcg gtatctctcc 43380 gcgtgaggcg ttggcgatgg atccgcagca gcggttgctg ttggagacgt cgtgggaggc 43440 gttggagcgg gcgggcatcg atccgcacac gctccgcggc tcacggaccg gcgtctacgc 43500 cggagtgatg taccacgact acggcagcac cgcgaccgtc tccgtcgcct ccgacgacga 43560 gaccgccgga ttcctcggca cggggacgtc cgggagtgtg gcttcgggtc gtatctcgta 43620 tgtgctgggg ctggaggggc cggcggtgac ggtggacacg gcgtgttcgt cgtcgttggt 43680 ggcgctgcat ctggcggtgc gggcgctgcg gagtggtgag tgtgaccttg ctcttgcggg 43740 tggggtgacg gtgatggcgg agccgggtgt gttcgtggag ttctcgcggc agcgggggtt 43800 ggctgcggac gggcggtgca aggcgttcgc ggctgctgcc gatggcacgg gctgggccga 43860 gggtgtgggc gtgctggcgg tggagcggtt gtcggatgcg gtgcgtcacg ggcgccgggt 43920 cctggcggtc gtgcgtggtt ccgcggtcaa ccaggacggt gcgagcaatg ggttgacggc 43980 tccgaacggt ccgtcgcagc agcgggtgat tcgtcaggcg ttggcggatg cgcggttggg 44040 tgtggctgat gtggatgtgg tggaggggca tgggacgggg acgcgtctgg gtgatccgat 44100 cgaggcgcag gcgttgttgg cgacgtatgg gcagcgggat gcgggtcggg ctttgcggct 44160 tggttcgctg aagtcgaacg tggggcatac gcaggcggct gccggtgtgg cgggcgtgat 44220 caagatggtc atggcgatgc ggcacggtgt cctgccgaag acgctgcacg tggatgagcc 44280 gacggcggag gtggactggt cggcgggcgc ggtgtccctg ctgagggagc aggaggcgtg 44340 gcctgaggtg gggcgtctgc gtagggctgc ggtgtcttcg ttcggtgtga gtgggacgaa 44400 cgcgcatgtg gtggtggagg aggcacctgc ttcggaggcg ccggtcgcgg gggagccggt 44460 ggagccggtg gagccggggg ctgtggggct tcttccggtg gtgccggtgg tggtgtcggg 44520 tcgttctgcg ggtgcggtgg cggagctggc ctcccgcttg aacgagtcgg ttcgttcgga 44580 tcggttggtg gatgtggggt tgtcgtcggt ggtgtcgcgg tcggtgttcg agcaccggtc 44640 cgtggttctg gcggaggact ctgccgagct gcataccggt ctggttgctg tcgggactgg 44700 ggtgccgtcg cctggcgtgg tgtcgggtgt ggcgtcggtc gagggtggcc ggtcggtgtt 44760 cgtgttccct ggtcagggga cgcagtgggc ggggatggcg ctcgggttgt gggcggagtc 44820 ggcggtgttc gcggagtcga tggcgcggtg tgaggcggcg ttcgccgggt tggtggactg 44880 gcgtctggcg gatgtgctgg gtgacaggtc tgcgttggag cgggtcgatg tggtgcagcc 44940 ggcgtcgttc gcggtgatgg tgtcgctggc cgagctgtgg cggtcgctgg gtgtggtgcc 45000 cgatgcggtg gtggggcatt cgcaggggga gatcgctgct gcggtggtgg cgggtggtct 45060 ctcgctggag gacggcgcgc gtgtggtggt gttgcgtgcg cggttgatag gccgtgagct 45120 ggccgggcac ggtgggatgg cgtcggtggc gctgccggtc gcggtggtgg aggagcgtct 45180 ggcggcgtgg gcggggcgtc tgggtgtggc ggtggtcaac gcaccctccg ccacggtcgt 45240 cgcgggtgat gtggacgcgg tggcggagtt tgtgaccgcg tgcgaggtgg agggggttcg 45300 ggcgcgtgtt ctgccggtgg actacgcctc gcactcggcg cacgtggagg agctgagggc 45360 cgagcttgaa cagattctgg ccggcatcga cccggtggcc ggtgagaccc ccctgtactc 45420 cacggtggag gcgggtgtcg tggatacggc gtcgatggat gcggggtact ggttcaggaa 45480 tctgcgtcgg ccggttcgtt tccaggagac ggtcgagcgg ttgctggcgg atggtttccg 45540 ggtgttcgtg gagtgcggcg cgcatccggt gctgacgggg gcggtgcagg agaccgcgga 45600 atccaccggt cgccaggtgt gtgcggtcgg atccctgcgt cgtgacgagg gtggtctgcg 45660 acgcttcctg acctctgcgg cggaggcgtt cgtccagggg gtggaggtgt cctggccggt 45720 gctgttcgat ggcaccggcg cccgcacggt cgacctgccc acctacccct tccagcgtcg 45780 gcgttactgg ctggagtcac gtcctcctgc ggcggttgtt ccgtcggggg tccaggacgg 45840 attgtcgtat gaggtggtgt ggaagagcct gccggtacgg gagtcgtcgc gtcttgacgg 45900 ccggtggctg ctcgtcgtgc ccgaaaccct ggacgccgac ggcacgcgga tcgcccacga 45960 cctccagcac gccctcacca cccacggcgc caccgtgcac actcttgctc ttgaccccag 46020 cgcggcgcac ttcgacggtc tctttgacgg gatactccag gaagaaacag atgtcacggg 46080 catcttctct ctcctcggac tggcatcggg cccgcacccg gatcacggcg aggtggagct 46140 cgcgggagcc gcgtcgctga cgttgatgcg ccaagcccag cgagacggct tccgtgctcc 46200 ggtgtgggcg gtgacgcggg gtgcggtgtc cgtggtgcct ggtgaggtgc cggagaccgc 46260 gggtgcgcaa ctgtgggcgc tcggccgggt cgccggtctc gaactccccg accgttgggg 46320 tggtctgatc gatctcccgg cggatgccga tgcgcgtacg gcggggcttg cggtgcgggc 46380 cctggccgcc gggatcgccg atggtgagga ccagctggcg gtgcgcccct caggtgccta 46440 cggccggcgc ctcgtacgag ccaccgcgcg ccggggacgg aaggactggc gcccgcaggg 46500 tacggtgctg ctcgccgggc acctcgacgc cgtcggtgaa ccactggccc gatggctgct 46560 caccggcggc gcggaccacg tcgtccttgc ggatcccgcc ctgaccgaac tcccggccac 46620 cctcgcggat ctggcccaga ccgtgacgac cgctgcggca cccgaccttg ccgaccgtgc 46680 agtcctcgcc gccctggtca ccgagtacgt acccgccacc gtggtcgtcg ttccgcccgc 46740 ggcggagctc gctccgctgg cgagtatcag cccggccgac ctcgcggcgg ccgtcaccgc 46800 caagtccgcg accgcggcgc acttcgacgc gctgctcgac ggaccccacg caccggagct 46860 ggtgctgatc tcctcggtcg cggggatctg gggtggtgtc cggcagggtg cgtacgccgt 46920 cggtgccgct cacctcgatg ccctggccgc ccgccgcagg gcccgcggtc tgtcggcggc 46980 ctccgtcgcg tggacgccct gggcgggttc cgtcaccgcg gacggctccg ccgccgagtc 47040 gctgcggcag tacggcatcg ctccgctgga gccgcaggcg gcgctcgcgg agctggaccg 47100 ggcgctgaac cagcagctgc acggcggcgg gggcgacgcg gcggtggccg acatcgactg 47160 ggagcggttc ctcgcgtcgt tcacctccgt acgtcccagc gttctcttcg acgagctgcc 47220 cgaggtacgc cgtctccgcg aggcggaggc ggcggccatg gcggaccagg ccgccgcccg 47280 gacgggagcg cccggcggaa cggagctggc gcgctctctg cgggccaagt ccctgaacgc 47340 ccagcgaact gcgctcctgg aattggtcac tgcccacgtg gcggccgtgc tgggagagag 47400 cgttcccgag gcgatcgacc ggagccgggc gttcaaggac atcggcttca cctccatgac 47460 cgcgatggaa ctgcgcaacc ggctcaagga ggccaccggg ctcgcccttc ctgcctccct 47520 cgtcttcgac cacccccacc ccggcgcact cgccgaccac ctgcgcgagg aactcctggg 47580 cgaggacggt gcggcgggcg ccgactccgc ggcggaggaa ccgagcgcta cctctccgac 47640 ggtccaggac gagccgatcg ccatcatcgg catggcctgc cgcctccctg gtgacgtcgg 47700 aacacccgac gaactctggg agctgctgga aaccggccgc gacgcgatgt cggacctgcc 47760 cgtcaaccgc gggtgggacg tggcggggct ctacgacccg gatccagacg cggcggggcg 47820 ttcctacgtc cgggagggcg ggttcctcca cgacgcgggg gagttcgacg cggagttctt 47880 cggcatctcg ccgcgtgagg cgctggcgat ggacccgcag cagcgcatcg tcctcgaact 47940 cgcctgggaa tcgttcgaac gtgcgggcct ggacccggcc ggccgccgcg gcagccgtac 48000 cggcgtgttc atgggaacca acggccagca ctacatgccg ctgctgcaga acggcaacga 48060 cagcttcgac ggctacctcg gcaccgggaa ctcggccagt gtcatgtcgg gccgcatctc 48120 gtacaccctc ggcttggagg ggccggcgct gacggtggac acggcgtgtt cgtcgtcgct 48180 ggtcgcgctg catctggcgg tgcgggcgct gcgcaacggt gagtgcgacc tcgccctcgc 48240 cggcggcgcg accgtgatgt cgacgccgga agtcctggtg gagttctccc ggcagcgtgc 48300 agtctccgca gacggtcgct gcaaggcgtt ctccgcctcg gccgacggct tcggaccggc 48360 cgagggtgcg ggcgtgttgc tcgtcgagcg gttgtcggat gcggtgcgtc atgggcgtcg 48420 ggtgttggcg gtcgtgcgtg gttcggcggt gaatcaggac ggtgcgagta atgggttgac 48480 ggctccgaac ggtccgtcgc agcagcgggt gattcgtcag gcgttggcgg atgcgcggtt 48540 gggtgtggct gatgtggatg tggtggaggg gcatgggacg gggacgcgtc tgggtgatcc 48600 gatcgaggcg caggcgttgt tggcgacgta tgggcagcgg gatgcgggtc ggccgttgcg 48660 gcttggttcg ttgaagtcga acgtggggca tacgcaggcg gctgccggtg tggcgggcgt 48720 gatcaagatg gtcatggcga tgcggcacgg tgtcctgccg aagacgctgc acgtcgatga 48780 ggtctctccg cacgtcgact ggtcggcggg tgcggtgtcc ctgctgacgg agcaggagcc 48840 gtggccggag gtggggcgcc ctcgcagggc tgcggtctct tcgttcgggc tcagcgggac 48900 gaatgcgcat gtggtggtcg aggaggcgcc ggtcggggag gcggggcagg ccgccgggga 48960 tgctcggttg gctgtggtgc cggtggtggt gtcgggccgg tctgcgggtg cggttgctga 49020 actggcctcc cgcttgaacg agtcgattcg ttcggatcgg ttggtggatg tggggttgtc 49080 gtcggtggtg tcgcggtcgg tgttcgagca ccggtccgtg ctactggcgg gggactctgg 49140 cgagctgcat accggtctgg ttgctgtcgg gactggtgtg ccgtcgcctg gtgtggtgtc 49200 gggtgtggcg tcggtcgggg gtggccggtc ggtgttcgtg ttccctggtc aggggacgca 49260 gtgggcgggg atggcgctcg ggttgtgggc ggagtcgtcg gtgttcgcgg agtcgatggc 49320 gcggtgtgag gcggcgttcg aggggttggt ggactggagt ctggcggatg tgctgggtga 49380 cgggtccgcg ttggagcggg tcgatgtggt gcagccggcg tcgttcgcgg tgatggtgtc 49440 gcttgctgag ctgtggcggt cgttgggtgt ggtgccggat gcggtggtgg ggcattcgca 49500 gggggagatc gctgctgcgg tggtggcggg tggtctgtcg ttggaagacg gggcgcgtgt 49560 ggtggtgttg cgtgcgcggt tgatcggccg tgagctggcc gggcgcggtg ggatggcgtc 49620 ggtggcgctg ccggtcgcgg tggtggagga gcgtctggcg gggtgggcgg ggcgtctggg 49680 tgtggcggtg gtcaacggac cgtccgccac ggtcgtcgcg ggtgatgtgg atgcggtggc 49740 ggagtttgtg accgcgtgcg aggtggaggg ggttcgggcg cgtgttctgc cggtggacta 49800 cgcctcgcac tcggcgcacg tggaggacct gaaggccgag cttgaagagg tgctggccgg 49860 catcggcccg gtgaccggtg ggatcccgtt ctattcgacg tccgaagccg cgcagatcga 49920 cacggctggt ctggacgcgg ggtactggtt cgggaatctg cgtcggccgg tgcggttcca 49980 ggagacggtc gagcggttgt tggcggatgg tttccgggtg ttcgtggagt gtggtgcgca 50040 tccggtgctg acgggggcgg tgcaggagac cgcggaatcc accggtcgcc aggtgtgtgc 50100 ggtcggatcc ctgcgtcgtg acgagggagg tctgcgccgc ttcctcacct ctgcggcgga 50160 ggcgttcgtc cagggggtcg gggtgttctg gccggcactg ttcgacggca ccggcgcccg 50220 tatcgtcgac ctgcccacct accccttcca acgacggcac tactggtaca acgaccctgc 50280 ccgccgcacg ggcgatgcca cctccttcgg tatggcgcag gccggtcatc ccttgctcga 50340 tgccggtacg gagctccctg aatcaggcga gcacctctac accgctcggc tcgccgccga 50400 ctcgcatcct tggctgctgg aacacaccct gctgggtgcg ccgttgctgc ccggtgcggc 50460 gttcgtcgac ctcgtcctgt gggccggcgg ggaggtcgga tgcgacctga tcgaagagct 50520 gacgctgacc tcgccgctgc tgttgtccga cagcgctgcc cttcaactgc ggctggtcgt 50580 gggcacggcg gacgccgagg gacgtcgtac gatcaccgtc cactcgcggc cggacggaga 50640 cccgcgtacg acgcgcacac ctgcggcatc gtccgagacc agcccggacg cggagtcgga 50700 cacggagatc cgtagggaca cgtccgcctg gacgaagcac gctcaggcga cggtcgcccc 50760 cgcccctgac gtcccccctt ccggggtgga cgcggaaggg gacgccgttc gccccgcagt 50820 ggaatggagc gtggcggcga cggagtcgga tgccttccag gccgaggact tctacgcgtc 50880 cttcgccgca cacggctatg gctacggccc gctgttccag ggcgtacggt caggccgtca 50940 ggacgggacc gacgtctacg ccgaagtcgc cctggatcac gaccgcttgc cgtctgccga 51000 gcagttcggc ctgcaccccg cgctgctcga cgcggcgttc cagacgatgc gtctgggatc 51060 gttcttcccc gacgacggac aggcacgtgt gccgtacacc ttccggggga ttcgtctcta 51120 cgccccggga gccgcgcgcc tgcgggtccg tgtctcggcg gtcggggccg atgccgtacg 51180 cgtggagtgc gccgatgagc gggggcggct cgtctgtgag atcgacgccc tcgtcgtcag 51240 cacggtctcc ccggaccagt tgcggccggc cggacaggac gcgacccagg acatgctgca 51300 ccggatcgag tggcccgtcc tctccccgcc gaccggcagc gccacctccc ctgctccgcc 51360 ccgctggatc gtggtcgggg gcgaggacga gggcctcggg ctcgggggcc ttcgactcga 51420 cggtccgagg cttgacggtc ccgggcttgc ggaagcgctg tccgaagccg gtatggggac 51480 cgagcgtcac cggaacctgg ccgacgcgct gtcggccgta cggacgccgg tggacacggc 51540 aggctccgct gccgccgccg gcacgacctc cctcatagcc gtccccgtac cgcagtcgcc 51600 caccatggac gccggtgccg tgcgccacgc cgtccaccga gccctggagc tggtgcaggg 51660 ctgggtggcg gcggacgagg cggcggaaga gggcgggagc gacggtgccg cggccgaccg 51720 gcggctggtg ctggtcacga gcggagcggt gtccacgggt gacgccgacc cgctgcgcga 51780 cccggtggcc gcggccgtct ggggtctgat caagtccgcc cagtcggagc agcccggccg 51840 catcgtcctc gttgacctcg acgagggagc cgtggacggg gcggccttgg cagccgcgat 51900 ctcgaccggc gaaccacaac tcgccctgcg cgacggcgat gtgcacgtgc ccaggctggc 51960 acccctgtcc gtgcgggact cgcagacgct gctgccgccc gccggtacgc gcgcctggca 52020 tctggtcggc gccggcaccg gaaccctttc ggacctcgcg ctcgtaccgg cgcagaccga 52080 caccgtcgcg ctcgcacctg ggcaggtgcg gatcgcggtg cgagccgccg gactcaactt 52140 ccgggacacg ctcatcgcgc tcggtatgta tccgggcgag ggcgtgatgg gcgccgaggg 52200 cgccggagtg atcaccgagg tcggcccgga cgtggtgagc ctcgccgtcg gggaccgcgt 52260 cctgggcatg tggaccgacg ggttcgggcc gtacgtcgtg gccgaccacc gcatggtggc 52320 cccgatgccg cgcgactggt cctacgcgga ggccgcttcg gtacccgccg tcttcctcag 52380 tgcctactac ggactcaggc acctggccgg tctgcgcgcc ggccagtcgg tgctggtgca 52440 cgcggcggcg ggcggtgtgg gcatggctgc cgtccaactc gcccggcact tcggggccga 52500 ggtcttcggc acggccggca cggccaaatg ggacgcactg cgggcacagg gcctggacga 52560 ccggcacatc gccggttcac ggacgctgga cttcgcggac cggtttctcg acgcgaccga 52620 ggggcgcggc gtggacgtcg tcctgaactc gctggcgggc gacttcgtcg acgcctccct 52680 gcgactgctg ccgcgcggag ggcggttcgt ggaactgggc aaggcggacg tacgcgacgc 52740 cgcgcaggtc gccgccgacc ggccgggaac cgtctaccgg gccttcgagc tgatggaggc 52800 cgggccggag ctgatcggcc gcatgctgaa cgaactgctg gaactgttcg agtccggggc 52860 gctgcgcctg ctgcccgtca ccccgtacga catccggcgg gcacccgacg ccttccgcac 52920 gctcagccag gccggtcacg tcggcaaact ggtcctgacg atgccaccgg ccttcgaacc 52980 ccacggcacg gtcctgatca ccggcggcac cgggaacctg ggcggaacac tcgcccgcca 53040 tctcgtgacc gaacacggag tgcgccacct gctcctggcc ggacgtaggg ggcccgaggc 53100 cgaaggcgcc gccgaactcg tacgggaact gcacgacctg ggcgcctccg tcacggtcgc 53160 cgcctgtgac gtggccgacc gagcggcgct ccggaaactc ctcggcggca taccgccgga 53220 gcgcccgctc accggagtcg tccacgcggc gggcgttctc gacgacggcg tggtcacgtc 53280 attgaccccg gacagggtcg acggcgtcct gcggcccaag gtggatgccg ctctcaacct 53340 ccacgaagcg gccctcgatc ccgaactcgg tctcgacatc accgcgttcg tcctgttctc 53400 gtccgtcgct gccctgctcg gcggctcggg tcagggaagc tacgccgccg ccaacggctt 53460 cctcgacgga ctcgcccagt accggcgtgg ccgctcgctg cccgcgctct ccctcggctg 53520 gggcctggcc gggagcggcc ggatgacatc ccacctggac agccgggccc tgctccggcg 53580 catggccagg ggcggtgtcc tgccgctgtc cccggcggag agcatggcac tgttcgacgc 53640 ggcccagggc ttcgacgagg cgctccaggt gccggcgcgc ttccacaccg ccgcactggg 53700 cgccgacggc aacgtcccgc cgctcttcaa cggactgatc cggggcggga cggcgcatgc 53760 cgaggcccgg cgcaggacgg tcggcgcgtc gcccgcgggt ggtcctgccg gaggcgagcc 53820 ggtgaacctc gccgaccggc tgtccggact gacggaggac gaacagcggg cgctgctcct 53880 cgacacggtg cgcacgcacg cggctctcgt cctgggccac acgggcacgg acggcatcca 53940 ggccgaccgg gcgttcaagg acctgggatt cgactcgctg acggccgtcg agatgcgcaa 54000 ccggctcacc gccgccacgg ggctgcacct cgcggcgacg ctggtcttcg accaccccgc 54060 tccggcggac ctcgccgagc acctccgctc tcgactcgtc cccgagggga cggacgtacc 54120 gccgctcctc gcggaactcg gtcggctcga aacggcgttc aagaagctga ccaccgcgga 54180 cctcgcctcg gtcgtgcccg acgacatcgc ccgcgacgag atcgccgtac gtctcgccgc 54240 cctcggttcc ctgtggaacg ggctccatgg caacggcctc agcggagacg cggcgcagaa 54300 gcacggcgac tcgatcgtcg aggacatcga ctccgccgac gacgacgaga tcttcgcctt 54360 cctcgacgag agcttcggcg actcctgacc gcaggcacct ccgtacggac cgacgactct 54420 gcagacgggt gatgagagat ggcgaccgaa cacgagcaga agctccgcga ctacctcaag 54480 cgggccacca ccgaactcca caaggccacg gaacggctga aggaggtcga acaacgcgct 54540 cacgagccgg ttgcgatcgt ggggatggga tgccggttcc cgggcggggc gtcctcgcct 54600 gaggagttgt gggacctggt ggcggcggag acggacgcgg tctccccctt cccggtggac 54660 cgggggtggg acgtgacggg gctgtacgac ccggatccgg acgcggcagg gcgtgcctac 54720 gtccgcgagg gcgggttcct ccacgacgcg ggggagttcg acgcggggtt cttcggaatc 54780 tctccgcgtg aggcgttggc gatggatccg cagcagcggt tgctgctgga gacgtcgtgg 54840 gaggcgttgg agcgggcggg catcgatccg cacacgctgc gcggcacgcg gaccggggtc 54900 tacatgggtg cctggaacgg cggatacgcc gaggggattc cccaacccac ggcggaactg 54960 gaggcccagc tcctcaccgg cggcgtggtg agcttcacct cgggccgtgt gtcctacctc 55020 ctgggtctgg aggggccggc ggtgacggtg gacacggcgt gttcgtcgtc gctggtcgcg 55080 ctgcacctgg cggtgcgggc gctgcgcagt ggtgagtgcg acctcgccct cgccggcggc 55140 gcgacggtga tgtcgacgcc cgacgtgttc gtgcgcttct cccggcagcg aggagtggcc 55200 gcggacggtc gctgcaaggc gttctccgcg tcggccgacg gattcggacc ggctgagggt 55260 gtgggcgtgc tggcggtgga gcggttgtcg gatgcggtgc gtcatgggcg tcgggtgctg 55320 gcggtcgtgc gtggttccgc ggtcaaccag gacggtgcga gcaacggact gacggcgccg 55380 agcggacgag ctcaggccct tctgattcgt cgagcgttgg cggatgcgcg gttgggtgtg 55440 gctgatgtgg atgtggtgga ggggcatggg acggggacgc gtctgggtga tccgatcgag 55500 gcgcaggcgt tgttggcgac gtatgggcag cgggatgcgg gtcggccgtt gcggcttggt 55560 tcgttgaagt cgaatgtggg gcatacgcag gcggctgccg gtgtggcggg cgtgatcaag 55620 atggtcatgg cgatgcggca cggtgtcctg ccgaagacgc tgcacgtgga tgagccgacg 55680 gcggaggtgg actggtcggc cggcgcggtg tctttgctga gggagcagga ggcgtggcct 55740 gaggtggggc gtctgcgtag ggctgcggtg tcttcgttcg gtgtgagtgg gacgaacgcg 55800 catgtggtgg tggaggaggc gccggttccg gaggacgggg aggcggtcgg gggcggtgtg 55860 cctttggctg tggtgccggt ggtggtgtcg ggtcgttctg cgggtgcggt ggcggagctg 55920 gcgggccggg tcagcgaggt ggctgcgtct ggtcggttgg tggatgtggg gttgtcgtcg 55980 gtggtgtcgc ggtcggtgtt cgagcaccgg tccgtggtac tggcggggga ctctgccgag 56040 ctgaatgccg gtttggatgc tgtggccggt ggtgtgccgt cgcctggtgt ggtgtcgggt 56100 gtggcgtcgg gtgagggtgg ccggtcggtg ttcgtgttcc ctggtcaggg gacgcagtgg 56160 gcggggatgg cgctcgggtt gtgggcggag tcgtcggtgt tcgcggagtc gatggcgcgg 56220 tgtgaggcgg cgttcgtcgg cttggtggac tggcgcttgt cgcaggtttt gagcgatggg 56280 tcggcgctgg agcgggtgga ggtggtgcag ccggcgtcgt tcgcggtgat ggtgtcgctt 56340 gctgagctgt ggcggtcgtt gggtgtggtg ccggatgcgg tggtggggca ttcgcagggg 56400 gagatcgctg ctgcggtggt ggcgggtggt ttgtcgctgg aggacggggc gcgtgtggtg 56460 gtgttgcgtg cgcggttgat cggtcgtgag ctggccgggc gcggtgggat ggcgtcggtg 56520 gcgctgccgg tcgcggtggt ggaggagcgt ctggcggggt gggcggggcg tctgggtgtg 56580 gcggtggtca acggaccgtc cgccacggtc gtcgcgggtg atgtggatgc ggtggcggag 56640 ttcgtggccg cgtgcgaggt ggagggggtt cgggcgcgtg ttctgccggt ggactacgcc 56700 tcgcactcgg cgcacgtgga ggacctgaaa gccgagcttg aacagattct ggccggcatc 56760 ggcccggtga ccggtgggat cccgttctat tcgacgtccg aagccgcgca gatcgacacg 56820 gctggtctgg acgcggggta ctggttcggg aatctgcgtc ggccggtgcg gttccaggag 56880 acggtcgagc ggttgttggc ggatggtttc cgggtgttcg tggagtgtgg cgcgcatccg 56940 gtgctgacgg gggcggtgca ggagaccgcg gaatccaccg gtcgccaggt gtgtgcggtc 57000 ggatccctgc gtcgtgacga gggaggtctg cgccgcttcc tcacctcggc cgcggaggca 57060 ttcgtccaag gcgtggaggt gtcctggccg gcactgttcg aaggcaccgg cgcccgcacg 57120 gtcgacctgc ccacctaccc cttccaacgt cggcgctact ggctggagtc gcgccctccc 57180 gcggcgccga tcgagactgc cgcagcctct ggcatcgaga gctggcgcta ccgcgtggcg 57240 tggaagagcc tgtcgctgtc ggagtcgtcg cgtcttgacg gccggtggct gctcgtcgtg 57300 cccgaaaccc tggacgccga cggcacgcgg atcgcccacg acatccagca cgccctcacc 57360 acccacggcg ccacggtctc ccgtctgacg gtcgacgtga cgacgaccga ccgcgccgac 57420 ctgtcggcgc ggctcaccac caccgcggcc gaagaccagg ggcctctccg gggcgtcctc 57480 tccctcctgt ccaccgatga acggcagcac ccggatcatc ccggtgtcga ccgtgccacg 57540 gcgggcacga tgctgctcgc ccaggcgtgc ggggatctgg tcgtggcccg gggcgtggag 57600 ccgaggctgt gggtcgtgac ccgcggggcg gtcgcggtgt cccccgccga gcgtccgtcg 57660 tcagccggcg cccaggtctg gggcctgggg cgctgcgcgg cgctcgaact tcccactcgg 57720 tggggtggga tggtcgacct tcccccggcg gcccgggatg ctggaaggca cgtacggcgg 57780 ctcgtgcgtc tgctgtcgga gacctgtgcg gaggaccagg tggcgctgcg tgcgtcgggt 57840 gcgtacggcc gcaggctgct gcccgcgtcc agcccctccg tatccgtccc ccggaccgcg 57900 aagagcggct accagccgcg cggcacggtg ctggtgaccg gcggaaccgg tgccctcggt 57960 ggccacttgg cacggtggct ggcccgcaac ggcgccgagc acatcgttct ggccgggcgt 58020 cggggcgagg gtgctccagg agccgcggaa ctgtcggcgg agctcaagga gctgggtgcg 58080 gaggtcaccg tcgcggcctg cgacgtggcg gaccggaacg cgttgcgtga catgctggaa 58140 tccctgccgg ccgaccggcc gctgtcgggg gtgttccacg ctgccggtgt cccgcactcg 58200 gcgccgctgg ccgagacgga tgtggcgggg ctcgccgccg tgctcccggg gaaggtcgtc 58260 ggggcacggc acctgcacga actcaccagg gagaaggaac tggacgcgtt cgtgctgtac 58320 gcgtcgggcg ccggggtgtg ggggagcggc gggcagagcg cgtacggagc cgccaacgcc 58380 gcactggacg cgctggccga acagcgccgg gctgagggac tgcccgccac ttcggtctcc 58440 tggggcctgt gggacggcgg aggcatggcc ggcgagcgag gcgaggagtt cctcaccgcc 58500 ctcggcctgc gggccatgga gcccgagtcg gctgtcgccg ccctggagga ggccctggat 58560 cgtggggaca cctgcgtgag cgtggtcgac gtcgactggt cccggttcgc cgagtcgttc 58620 accgccttcc ggcccagccc gctgatcggg gagctccccg gggtacgtgc cgtgcccgac 58680 ggatcggcgg gcggaccgtc ggacgacctc gcggacgctg cgcggcacgg cggggcagcc 58740 gaccggggtg tgcctgcagg gctcgcccgg gcgacgggcg acgaccggca ggacatcctg 58800 ctcgatctcg tacgccgcca tgccgccgcc gtcctcggtc acccgggacc gcagcacatc 58860 gagcccgacg ccggtttccg gaccctgggg ttcagttcgg tcaccgcggt ggaactggcc 58920 aacaagctcg gtgcggccgt gggaacgaag atccccgcca ccttcgcgtt cgaccacccc 58980 aacgcccgtg ccgcggcgtc ccgcctcgac gtcctgttgg cggcgtcgag cgatgagacc 59040 gcgcaggagg cggagatccg gcaggcactg cggactgtgc cgctggcccg gctgcgggct 59100 gcggggctcc tcgacggcct gctcgaactc gccgggctgg aagcggagcc cggcctgccg 59160 ggcgacgtac cggatcgcgg tgcggccacg ccggacgagg agtccgccct ggcggaagtc 59220 gacggcctgg acgccgaagc actggtcgac ctcgtcctca accagtccga ctcctgaccg 59280 ccggcggcgg cgccgcggcc cgccgtgccg tcgccgccct cggccgtacg aagaacccca 59340 cagacctgac cgggtcacgg cccggtgctc agcaaggaga ccactcatgg ctctgtccca 59400 agagaaggta ctggaggcac tgcgcacctc cgtcaaggac gccgaacggc tgcgcaagcg 59460 caaccgcgaa ctcctcgcgg cccgccacga gcccatcgcc gtcgtcggca tggcctgccg 59520 ctatcccggc ggggtccgtt cgcccgagga cctctgggaa ctcgtcgtgt cgggcacgga 59580 cgcggtgggt ccctttcccg aggaccgtgg ctgggacgtg gagcggatct acgaccagga 59640 cccgtccgtc ccgggcacca cgtactgccg cgagggcgga ttcctttacg atgcggggga 59700 cttcgacgcg gctttcttcg ggatagggcc gcgcgaggcc accgtgatgg acccccagca 59760 gcgccagctg ctggaggcgt cctgggaagc cctggagcag gccgggctgg acccccgggc 59820 gctccgcggc agccaggggg gtgtgttcgt cggcgcggcg aaccagggct acgtaccggg 59880 tgacgcggcg gcgtcgggac gtctgccgga gggttccgac ggctatctgc tcaccggcaa 59940 cgccgacgcc gtcctgtcgg gccggatcag ctacttcctg ggcctggaag gcccgtccat 60000 gaccgtcgag acggcctgct cctcctccct ggtggcactg cacctggcgg tgcaggcgct 60060 gcgccgtgag gagtgcgagt tcgccctggc cggaggggtc gccgtgctcg ccaacccggc 60120 cgcctacgtg gagttcgccc ggcagcgggg actcgccccg gacgggcgct gcaaggcgtt 60180 cgacgacgcg gcggacggta cgggctgggc cgagggcgtc ggcgtcctgg tggtggagcg 60240 gctgtcggac gcggtacgca aggggcaccg ggtcctcgcc gtcgtgcggg gcacggcggt 60300 gaaccaggac ggtgccagca gcggtctgtc cgtgcccaac gggccctccc agcagcgggt 60360 catccgccga gcgctggccg acgcccggct ggaggccggc cagatcgacg cggtggaggc 60420 ccacggcacc ggcactcggc tgggggaccc catcgaggcg caagccctgc tggacacgta 60480 cggagaggag cggagccccg aacgccctct gtgggtcggg tcgttgaagt cgaacttcgg 60540 tcacgcacag gcggcagccg gagtcggcgg cgtcatcaag acggtgatgg cgctccggca 60600 cggcctgctt ccccgcacgc tccatgtgac cagcccgacg cggcacgtcg actggggcga 60660 cggacaggtg cggctgctga ccgagccggt cgactggccg cggaccggcg ccccccggcg 60720 ggccgcggtc tcggcgttcg gcgtgagcgg caccaacggg cacatcatcc tcgaggaggc 60780 gccgccgccc acccggcccg aagcggtccg gcaggccggg gagcggcggc cggtcctggt 60840 cccgtggacg ctgtccggcc gtacgaggcc ggcgctgtgc cggcaggccg cgcgcctggc 60900 ggcgcacctc gaacagcacc cggacctcga cccgctggac gtcgggttct cgctcgccac 60960 gacgcgcacc cacttcgagc accgggccgt gctgctcgcg gacgccgcca ccgagggcgg 61020 ctcccgtgcc gacgcgctcg gggcgttgcg ggcgatcgcg gaggaccgcg acccgggcgg 61080 ggcggtacgg gacaccgcgc ggggcgaagg gcgtatcgcc ttcctgttct gcgggcaggg 61140 cagccagcgg cccggcatgg cggagcagct gtacgcgcag tacccggcgt tcgcgcggga 61200 actggacacg atcgcgacgc atctggacgc ccatctggac cgtccgttgg cgacggtgat 61260 gttcgcgccg gccggtacgg cggaggccgc gctgctcgac ggcacgcagt acgcccaggc 61320 ggccctgttc gccgtagagg tcgcgttgtt ccggctcttc gagggctggg ggctgcgccc 61380 cgacgtactg ctgggccatt ccgtgggcga gctggccgcc gcccacgtgg ccggggtgtt 61440 cgggccggcg gacgcctgct cgctggtcgc cgcacgcggc cggctcatgc aggagctgcc 61500 ggccggcggc gcgatgctct cggtccgtgc cgccgagcac gaggtgcggg agctgatcgc 61560 cgggcaggag gaccgcatcg cggtggcggc cgtcaacggg ccccgctccg tggtcgtatc 61620 cggggacgag gacgcggtct cggcgctcgc cgaggagctg accgaatacg gcgtgcgcac 61680 caagcgcctc aacgtcagcc acgccttcca ctccccacgt ctggactcca tgctggagac 61740 gttccgccgg gtcgcggaga cggtggagta ccgcgagccg acgctcgacg tgatcagcgg 61800 cctgaccggc cgcccggccg acgccgggga actcgccacc gccgactact gggtccggca 61860 ggcgagggag accgtccggt tccacgacgg ggtgcgcgcc gcgcacgcgc gcggcgtcag 61920 caccttcgtg gagctggggc cggacggcgt gctgtgcggc ctggccctgg agaccctggc 61980 ggaggagacc gacggggaag cggccgccga gacgcccggc cgggcgcggg cggcgctggt 62040 gcccgtgatg cgtcgggagc ggccggaggg cagtaccctc ctgacggcgc tcgccacggc 62100 ccacgcgcgc ggggcggagg tggactggtc ccggttctac gccgacaccg gcgcccgcca 62160 caccacactg cccacctatg ccttccagcg ccagcggttc tggctggaga cggcggcccc 62220 cgccgcgccc gcggcgggcc agggggccgg accggccgac ccgcaggaca gcaccggtcc 62280 ggccgcccgg cccacgctga cggaacagga cctcctcctg ctcgtgcgga cggaagcggc 62340 ggccgcactc ggccacgccg aactggagga cgtaccggcc gacagcctct tcggcgacat 62400 cggcttcgac tcgctcgcgg ccatcgaact gggcgccgcc ctgaccggcg ccaccgggct 62460 ggaagtgccg tcgtccctcg tcctcgacca ccccacgccc agggagctgg ccgcgcacct 62520 ggcagccgcc cggacggccg ccgacagcga cgacacgtcc cccgaaggcc cggacacggc 62580 cggtgagagc agcctgtcgg cgatgtaccg gcgggccgtg cggctcggcc gggccgagcc 62640 gttcatcggc acactcgccg aactcgccgc cttccggccc gtcttccccg ccgatcacac 62700 cctcgcggac ggcgagaccg tcggacaggc ggccgccgcc tggcagccgg ctccggtgcg 62760 cctggccacc acggacggtg agggaccgga gctgatctgc tgcgcgggta cggcggtggc 62820 gtcgggaccg gaggagttca ccgcgctggc cgcggccctg ggcgaccggc tgaccgtgtc 62880 ggcactgcgc cagcccggct tccgcgcgaa cgagttgctg cccggctccc tggacgggct 62940 gctcgacgcg caggcggacg cggtgctgcg gcacacgggt gacaggccct acgccctcct 63000 cggccactcg gcgggcgggg cgctggcgca cgcgctggcc tgccgactgg aggagctcgg 63060 cgcgggtccc gcggcgctgg tcctggccga cgtctatctg cccagctcgc cgggggcgat 63120 gggggtgtgg cgcaacgaga tgctcgactg ggtcatgcgg cgttccgtgg tgtccatcga 63180 cgatgcccgg ttgacggcca tgggcgccta caaccagatg ctcctggagt ggacaccgcg 63240 gcccacgaag gcgccggtcc tgttcctgcg cgcgacggag ccggtgaggc cgtggtccgg 63300 agaaccggag agctggcggg cgcactggga cggcggcgac cacaccgccg tcgacgtgcc 63360 cggcacccac ctgacgctga tgaccgagca cgcccgccac ctcgcggcga ccctccacac 63420 ctggctcggc accctgtgaa ccacgcccgg ggcggcttcg ccgcgcgtag gactgccgcc 63480 tcccccgact tccgtacacc gcgacacctt ggaggactcc cgtgacaacg cagtggacca 63540 ccccgtccgt gctcggccgc agactgcaac gcacctacgt ggggcactgg ttcgcaggaa 63600 cgcagggaga cccctacgcg ctgatcctgc gcgcccagcg ggacgacacc accccctacg 63660 aggaggacgt ccgcgcacgc ggaccggtgt tccacagcga ggtgctcgac acctgggtga 63720 tcacggacgg cgctctcgcc cggtccgtcc tgaccgacgc ccgcttcggc gggctgacgc 63780 gcgcgggagg acggtatcgc gcggagcttc tccctccggc gggccccgag gtcggtccgg 63840 cccgcgcagg ggtacgcggc ggcgtgcggg ccgacgccga tccggcggtg tcggcgcagg 63900 acgaggtggt ggtggaggcc ctcgccgagc agctctcacg caccctcctg ggcggactcg 63960 gcgacgactt cgacctcgtc gccgcctttg cgcgacgcct gccggcacag gtcctggcgg 64020 aattcctcgg gctgcccgca gccgcgcgca gccggttcga ggaactgctg gccggctgcg 64080 cccacagcct cgacagccgg ctctgtccgc agacgctcga catcacacgg accggcctcg 64140 gagcggcggc cgagctccgg gaactgctcg cgcgccacct cggcgggagc ggaccacgct 64200 ccgctcaagc ggcagtctcc ctggcagtcg aggtggccgc acccgccggc gcgctcatct 64260 gcaacgcggt cgaggcgctg agcagctctc ccgggcagtg gaacgccctc cgccagaacc 64320 cggagaaggc cgacgccgtc gtggcggaga cctggtggcg acgaccgccg gtgcgggtgg 64380 agagccggat cgcccaggag gacgtcgacg tggccggagt gcccgtcccc gcggacgggc 64440 acgtggcgat cctcgtcgcc gccgcccagc gcgacccggc gatcaccccg gccccgacga 64500 aggacgacac cggcaccccc ggacagggcg actgcggcgt gcccctgggg ctcgtcggcg 64560 acgcgcacgc cacctccgcc gcccggacgg tccgcgccct ctgccgcggt gcgctgcgag 64620 cgctcgcgca ggaggcaccg ggcctgcggc cgaacgggac cccggtgcgc ctcaggcggg 64680 cacccgtcac gctcggccac gcccgcttcc ccgtcgcccg gacgggccgg gggacaccga 64740 ccgacgcggg cgcggcatga gcacccgcga cgaccaccga ctgccgaacg gggagacgag 64800 ccgatgcgcg tcctgatgac gtcgatcgcc cacaacacgc actactacca cctggtgccg 64860 ctcgcctggg ccctgaaggc cgcgggccac gaggtgcgcg tcgccggcca gccccgcgtc 64920 acggacatca tcaccgggtc cggactgacc gccgtgccgg tcggtgacga cgaggacatg 64980 atggagctgt tcgccgagat cggcggagac atcaccccct atcaggaggg actggacttc 65040 gccgaggagc ggcccgaggc acggtcctgg gaacatctgc tcggacagca gaccgttctg 65100 acctcgctgt gcttcgcacc gctcaacggc gactcgacga tggacgacat cgtcgcgctg 65160 gcccgctcct ggcagccgga cctggtgatc tgggaaccct tcaccttcgc cggagcggtc 65220 gccgcccacg ccgtgggcgc ggcgcacgcc cgcgtcctgt ggggtcccga tgtcatcggc 65280 cgggcccggg aacggttcgt ggaggccaag gcacagcagg ctcccgaaca ccgggaggac 65340 ccgatggccg agtggctcgg ctggaccctg gagaggctgg gcctcccggc cgccggagac 65400 gggatggagg agttgctgaa cggccagtgg gtcatcgacc cgggcccgga gagcgtccgg 65460 ctcgaccttc gcgagccgat cctgcccatg cgtttcgttc cctacaacgg acctgccgtc 65520 gtccccggat ggctgtccga gaagccgaag cgaccgcgcg tctgcctcac ccagggagtg 65580 tcgggacgcg agacccacgg caaggacgcc gtccgcttcc aggacctgct cgcggcgctc 65640 ggcgacctcg acatcgagat cgtcgccacc ctggacagca cccagcggga gaacctgacg 65700 gaggtccccg acaacgtccg gatcgtcgac ttcgtctcga tggacgtgct gctgccgagt 65760 tgcgccatga tcatctacca cggtggcgcc ggcacctcgg cgacggccct cctgcacggc 65820 gttccgcagg tcgtcatcgg agcgcactgg gacgtgccgg tcagggcacg gcagctcgac 65880 gacctgggcg ccggcatctt catccggccc gaggacctcg acgccgccac actgcgcgcg 65940 gcggttcagc gcgtgctcac cgagccctcc ctccagcggg ccgcggaccg gctgcgggcc 66000 gagatgcgct ccaaccccac gccggccgag accgtcacgg tgctggagcg gctctcccgg 66060 agccaccgac agccccgctg accacacgcg gtacacggtg cgggcccacg tgccgggggc 66120 tccaccgtcg ccggcggtcg tcggatcgcc gtccggccat gtcccggcac ccaaggacgg 66180 agcagagcag aacatggaat tcgaaggtca ggtcgcgctc gtcaccgggg ccggcagggg 66240 gatcggccgt gcgacggtcg tccgcctcgc ggaggccgga tgtgacatcg ccctccacta 66300 caaccaagcg aaagcgcagg ccgaggaagt cgccgagcgc atcgccgcac tgggccgcac 66360 ggtcgaactg ttcccgggcg acctctcccg ccccgagacc gggcgacagc tcgtggccgc 66420 ggtgcagcag aagttcgacc ggatcgacat cctggtgaac agcgcgggca tcacacggga 66480 caaactcctg ctgtccatgg aggcggacga catccaccag gtcatcgcca ccaacctcgt 66540 cggcccgatg ttcctcaccc aggcggtcgc gctcaccatg ctgcgtcaac gctccgggcg 66600 catcgtcaac atctcctccg ccgccgcgag caggcccgga aagggccagt ccaactacgc 66660 cgcgtccaag gccggtctgg aggccttcac cagggccatg gcggtggaac tcggatcccg 66720 cggaattctc gtcaacgcgg tcgctcccgg catcgtcaag accggcctga ccgaggctct 66780 ccgcgagggg gcggagcccg aactcctggc ccggcaggtg atcggttcct tcgccgaacc 66840 cgaggcggtg gcggaggcgg tggcctactt ggcgagcccg cgcaacacgc acacgacggg 66900 cacggtcctc accgtcgacg gcgggctcaa gatggtgtga ggcccaccgg gcatcggaca 66960 gccggtggat ccgccggagg cggagacccg cgcaccgcgg gcgtcgaccc gcgcaccgcg 67020 ggcgcgcgtg ggggcgcccg cggtgcgcga aggccgcctc tggctcgcgt caccggaaga 67080 agcccgattc cccagcgggc gaccgtagcc ggagcgttgg accgccctgc tccgcacgtc 67140 gagccccacc gtggtagcgg cggacatgcc cagggggcgc acgcccggat cctgccgcac 67200 gaccaggcgc accagggttt cggcgaacac ggcggccgac gccgcggggt tgccgccgcg 67260 gcacggccga cgcgcgctgg tcgcacgggg tgagcccgcg ggagcggagg gcgccggttc 67320 gctcaggacg ccgggatctc cgccgggacg acggactcgg gggcgccgtc ggggccgggc 67380 ctcgtgccac cgtcggcgtc gagctgcggc ggatcggaga gctgctcgcg cacgtacccc 67440 cacaccacgg cgacgagggc ggcgacgggc acggcgagga ggctgccgac gatgcccgcc 67500 agactgccgc ccagggtgac ggcgagcagg acgacggcgg cgtgcagtcc gagtccgcgg 67560 ctctggatca tgggctggaa gacgttcccc tccagctgct gcaccaccac gatgatcgcg 67620 agcacgatca gggcgtcggt caggccgttg gagaccaggg cgatgagcac ggcgacgaat 67680 cctgctaaca gcgcgccgat gatcggcacg aaggcgctga cgaaggtgag tacggcgagc 67740 ggcaggacga gcgggacgcc gaggatccac aggccgatgc cgatgaggac ggcgtcgagg 67800 aggcccaccg cggcctggga gcggacgaag gcgccgaggg tgtcccagcc gcgttcggcg 67860 atcgtggtgg cgtcggtcgc gaggcggccg gggagctgac gggcgagcca gggcaggaag 67920 cgcggcccgt ccttgaggaa gaagaacatc aggaagagcg cgaggacggc cgtgacgacc 67980 ccgttcacca ccgtgccgac gccggtggcg agggtggtca gcagggatcc gacgctgttc 68040 tggagacggt cggtcgcggt gtccagggcg ccggtgatct ggtcgtcgcc gatgttcagg 68100 ggcggacccg cggtccactc gcggagacgc tggatgccct cgacgacacc gtcggccagt 68160 tcgccggact gcgaggcgac gggcacggcg atgagcgcga cggtgccggc ggtgacggcg 68220 aggaagagga cggtgaccac cgaggcggcg agcgccggcg gccagccgag acggcgcaac 68280 aagcgggcga agggccaggt cagcgtggtg atcagcagac cgatgacgag tggccacacg 68340 atcgaccaca tccggccgag cagccagatc accgccgccg tgcccaagag caccagcaga 68400 agctccgtcg atatgcgggc cgaggcccgt agcgcggcac gtgttctcgc aggactgaga 68460 gaggcagaca tggcgatcac cctagagcgg cccgggcggc ccgctgcccc cgtgccccga 68520 tccttcgcgc cggggtgacg cgcatcgggg gttccggcac tgcctgagcg cctgcacgga 68580 cggggcgggt tacgccgagg ggaagcagcc ggctccggat cgacaggagt gcgggtgacg 68640 gtcgtacacc ggcgctacgt cgcccactcc gcggcgcaca agggcggtcg ccgtctggcc 68700 cctccccgcg tccgacgacc gcccacccct cgtcagggag cggggtccgg ggcgaggtgg 68760 atacgggccg ctaccgggag gtggtcgctg gccgtcgcgg gaagggtcca tgccgaggcg 68820 gcccggacgc ccccgagaag gatctggtcg atccggacga ccggcaggcg cgccggccag 68880 gtgaagccga agcccgcgcc cgccgcggcc tgtgcggaga cgagacggtc ggtgaggggg 68940 cgcagtgcgc ggtcgtccgt ggagccgttg aggtcgccca ggaggacgac gcgccggacg 69000 ggctcggccc gcacctccgc cgccagcagc cccagcgcct cgtcgcgcgc cccggcggtg 69060 aatccgcccg ggcccacgcg gacggacggc agatgggcga catagacggc cagcggcccg 69120 ccgggcgcgt ccaccgtggc ccgcatcgcc cgcgtccacg gcatgatcgg cacagcccgc 69180 gcgtcgctca gcggatgcac gctccacaag cccaccgtgc cctcgtagaa gtggtacggg 69240 tacgactccg caagggcccg ctcgtaggcg ggcgccgtgg ccgggctcag ctcctccaac 69300 gccagtacgt ccgccccggc ggcgagcagg ctccgcaccg ttccggcggg gtcggggttg 69360 gcctgctcga cgttgtgact gaccagcgtg aggtccccac cgggcgtcgt cttgtcggtc 69420 agcgctccgc cgaaggccgt cagccaggcc acggccggca ccaccagggc caccaccgcc 69480 gccacccgcg cgcgccacag cagggccgcg gtcaccagca cgggcacggc cagcgcgctc 69540 cagggcagca aggtctctgc cagactgctc agccgtccgg gcagtccggg gagccgccca 69600 tggcccgcga cgctcaccgc gaggaagacg gaacagcccg tgaccgccgc cccgcggcgt 69660 cgccaccacc gccggcgcgg accggcgtcc cccacgccga ccgcggctcc gggagcgcgg 69720 cccctgccgt ccgccgtgcc gtccgcagcc agggagcaga cggtctgttc cgccctgccg 69780 tccgccgcag tggagggggc gctctccgct gccccgctgt ccggcgccgc gggggagggg 69840 acagtctgtg ccgccctgcc gtccggcgcc gcgaggaaga cggaacagcc cgtgaccgcc 69900 gccccgcggc gtcgccacca ccgccggcgc ggaccggcgt cccccacgcc gaccgcggct 69960 ccgggagcgc ggcccctgcc gtccgccgtg ccgtccgcag ccagggagca gacggtctgt 70020 tccgccctgc cgtccgccgc agtggagggg gcgctctccg ctgccccgct gtccggcgcc 70080 gcgggggagg ggacagtctg tgccgccctg ccgtccggcg ccgcggggga ggggacgggc 70140 tccgccgtcc cgccgtccgg caccgcggcc ggatcccggc gtgtcgtcgc cgtcatcgtt 70200 ccccgccctg ggttccggcg gcggccagcc gctcgcggac ggcggtgagc aggccacggg 70260 ccgcctcgac cgcggcccgg agcccctcgg cgggcgtcgt gttcgcccgc tggtgcagga 70320 cggcgcccac cagcagccgg ggcgcgccgc ccacgcgcac ctcgtaggcc cacaggaggt 70380 tcccgcccgc cggggtgctg gagcccgtct tcacaccgag gacgcccggg gtgtccagca 70440 ggggattggt gttggtgatc gtcccgaggc ccgggacggt ggtctcgcgg gtggcgacga 70500 ccgcccggaa gacagggtcc tccatcgcgg cccgcgtcag ccgcacctgg tcggccgcgg 70560 tgcttgtggt cgtcggctcg atgccgctcg cccccgtgta gaccgtgtcc ttcatcccga 70620 gccgtacggc ggcgcgccgc atcttcgtca cgaaggccgc ctggctgccg gagtcccagc 70680 gggccagcag acgggcgacg ttgttgccgg aggggatgag gagcagttcc aggagccggc 70740 gctgggagtg gcgttcgccg gaccgtaccg ggacggtcga ctcgccgccg acccccgcct 70800 cgtgcgcggc cgtccggtcc acttcgatca gggggccgtc ctcgtcgggc ctcagcggat 70860 gctcttcgag gatgacgtag gcggtcatca ccttcgtcag gctcgcgatc ggtacgggcc 70920 gccgctcgcc ccgctcgccc agcgagccgg ttccttcgag ctcgacggcg ctctggccgt 70980 cctgcggcca ggggagcggc ccgatgtcgg agaccggtag tcgctcgcct cccgccgccg 71040 gaggcgcgcc ggagggcgag gcgacggtga tgcccagggc cgtcagcagg gccacggaca 71100 gggcaccgcc gacgaggcgg tgacgggggg tgcggggcag ggacacgggc cgcctccagg 71160 ggctgcggta cgggatcggt acggcagcaa gactccgggg gctacgtctc cgcctcacgg 71220 tcgggagagc gcggcccgcg ctcgggaacc catcggtcgt gtatcggcgg ggcggcggcg 71280 accggccgcc gggcgacgcg gagggagcgc ctgaggggcg gggcgtaccg acaggcgacc 71340 gtctggggtg gggaggcccg cgggctgtcc cggggaccgg ttcacgcctc ggacgtctgc 71400 ccgtcctcgg gcaggctcag ggtcgcgacc gctcctccgt cccgggcgtt ggcgaaggcc 71460 agggtcgcgc cgatcaccct cgcctggccg gacgcgatcg tcaggccaag gccgtgcccg 71520 tgcccccgtt cggccgagcc cgtgcggaac cgctgggggc cgtgggacag caggtcggcg 71580 gggaagccgg ggccgtggtc ccggacggtc acggtccggc cggcgaccgt gacctccacc 71640 cgacccgcgc cgtgccggtg ggcgttgacg acgaggttgg agacgatgcg gtccaggcgc 71700 cgggggtccg actcgaccac tgccgccccc tgtcgcgtca cctgcgccgc gaggcccgtc 71760 cgcgccaccg agtcccggac gagggcgccc aggtcgaccg gtccctgctg ggccgtctcg 71820 gcgcccgcgt cgagccggga gacctccagg aggtcctcca ccaggtcgcg cagcacccgt 71880 acccggctct ggaccatgtc cgtcacctcg ccctcgggca gcagttccgc cgaggtgacc 71940 aggcccatca gcggggtgcg cagctcgtgt gcgacgtcgg cggtgaagcg ctgctcggtg 72000 tcgatccgct gctggaggct gtcggccatc gagtcgacca cggccgagat ctcggcgacc 72060 tcgtcgcctc cgcggaccgt tcccgtccgg gcgtcgaggt cgcccgccgt gatgcgccgg 72120 gccgtgcggg cgacccggcg cagccgccgg gcggggagtt ccgtcgccag ggccgtggcg 72180 gggacgacga cgcccagggt gagcagcgag tacttccaca tgtgacggtc cagggcctgc 72240 cgggtcagca ggtcggcggt catgtcgacc tcgaccgcgt acagcttccc gccctcccgg 72300 cgggccgccc ggaagacggg ggccgggggc ccgtcctcgt agagggtggc ctcgccgccg 72360 tgctcgatct gcctcagcag ggcctcgggc agttcctcgg gggacacccg gggcccttcc 72420 tcacctgctg cgtcggcgtc ctccaaggcc gttgccagcg ccacgtgggc cctgcccgcg 72480 ccctcgtgca gggagcgccg cagcaccgag tcgtgcacca gcactccgac ggtcagcgcc 72540 atcgaggcac aggcgagcgc caccaggagg acgatcttcc agcgcagcga gcgggagcgc 72600 ggtaccaggc ccgtgacggc tccccggggg gcccggctca ccgcttccac ttgtagccga 72660 agccccggac cgtctcgacg cgctcggcgc cgatcttctt gcgcagccgc tgcacgcaca 72720 ggtcgacgac ccgggtgtcc ccgtcccagc cgtagtccca cacctcgcgc aggagggtct 72780 gacggtccag cacgatcccg gggtgcgcgg cgaactggag cagcagccgc agctcggtcg 72840 gggcgagcgc gatccgctcg ccgccccggc ggacctccag ggccgcgggg tcgagggaga 72900 ggtcgccgaa gagcagcggg ccggccggcg tcgcggggtc ggcgggtccg ggggcggggg 72960 acacgaaggc ggcccggcgc agcagcgaac ggatgcgcgc caccaggacg gcggtgtcga 73020 cgggcttcac cacgtagtcg tcggccccgg cctccaggcc ggacaccacg tcgagggcgt 73080 caccgcgcgc cgacatcatc aggatcgggt ccgtggccgt ctcccggatg cgccggcaca 73140 gtccgatgcc gtccaggccc ggcagcatca cgtcgagcag caccaggtcg tgccgtccct 73200 cccggaagag ttcgagcccg gtcagtccgt cggccgcgac gcgcacgcgg tagccgtagc 73260 gctccaggga catcgcgacg gaccgccgga tcacctcgtc gtcctcgacc agcaggacgg 73320 tcacggtcgc aggcgcgggc gccgacacgg aatcagacat gtccatctct cgggcacggg 73380 gcggggcggg ccgacgcgcg gcccggccct ccatcatgcc tcactcgcgc gcctcccccg 73440 gcgccgccgg agagccgtcg gcacgcctct gagctggtct gatacctgac tgatacatca 73500 tggcgcggtg accgacacac gcccgagcgg ggacggacac ggaggcggcg cgccggacac 73560 aagatgccgc gggagccgat ccggcgccca ccgaggccgt gtgaacgacg ccgtccggaa 73620 ccgcacgccc gcgggggctc gtggcgggtg tcagtggtgt gcggcaggcg cgggcagcgt 73680 ctccggagcg gggtcggtcc tgcggccgag gtggttgaag gcgaggttga ggaggacggc 73740 gaccacacat ccggtgctga tgcctgagtc gaggacgatg cgggcgcctt cggggaaggc 73800 gtggtagaag tccggggcgg cgatggggat gatgccggcg cccagggaga tggcgacgat 73860 gaggacgttg tcgccgcgtt cgagggcggc tccggcgagg gtctggatgc cgctggcggc 73920 gacggtgccg aagagggcga tgcccactcc gccgaggacg ggctggggga tgagcgcgac 73980 gacggaggcg agcagcgggc agaggccgag caggaggagg atgccgccgg ccgcggctac 74040 gacgaagcgg ctgcggacct tggtgatcgc gacgaggccg acgttctggg cgaaggcgct 74100 ggcggcgaag ccgttgaaga gcgggctgag ggcggtgccg aggccgtcgg cgcggagcgc 74160 ggcggccagg gtcttctcgt cggccggccg ctcgacgatc tcaccgaggg cgaggacgtc 74220 ggcggtggac tcggtcatcg acacgagcat cacgatgcac atggagatga tcgccgcggc 74280 cgcgaactgc ggagcgccga agtggaacgg ggtggggagt ccgatgacgt cggcgtcgcc 74340 tacggcgctg aagtcggcga cgcccagcgg cagcgagagg agcgtgccgg cgacgaggcc 74400 cagcaggatg gagatctgct tgaggaagcc cgtcaggacg cggcgcagga ccacggtgat 74460 cagcagggtg gcggtggcga ggccgatgta cgtgaggctg ccgtagtccg gtgcctgcgc 74520 gttgccgccc tgggcccagt tgaacgcgac gggcagcagg gagacaccga tgagggtgat 74580 gaccgtgccc gtgaccacgg gcgggaagaa gcggatcagt ttgcagaaga agggggcgag 74640 gaggaatccg aagacgccgg cgacgatcac ggcgccgtag atgacgggca gcgcgtcgtc 74700 ggggccttcg gccttcgcta tcgcgagcat cggtgcgacg ccggcgaagg agacgccgtt 74760 gacgaacggg agccgtgctc cgaccttcca gaagccgagc gtctgcagga gcgtggcgat 74820 gcccgaggtg aacaggctgg cgctcatgag gaacgcgatg tccgcggtgg acaggccgac 74880 gccgatgccg acgaccagcg gcggcgcgac gacgccggcg tacatggcgg cgacgtgctg 74940 cagaccggcg ctgaagagct tcagcggggg cagcatctgg tcgaccggat gggtgtcgcc 75000 cggtcttgcg ggggtgtcgg gacgagcgtc ggttccgtcc tcggtcttcg tcggttccgg 75060 ggcggggcgg gattccggca tggcgtgtct cctggccgcg gcggtctcgt gggagcgcgg 75120 gcagccctgt gggagagccg gcgtcgctga cgcacggctc tgcggatggg ggtggtgacg 75180 gggtggggag gatgcggcac cgggcgtggg acgagaggcc gtcgtgcctg ggtgccgcgg 75240 ccggagagcg gggagtgggg cgccggagaa cgggcgggag ggattcgtgt cccggggttc 75300 ccgcggtcct ccggccggcc ggcgcgcagc tgtccgtgat gcgcgtcgtg ccactccgtc 75360 cggcgaagtc ggaacagttc ctcacggggc ggcgtgggtg tcaagaggcg ggacgggccg 75420 ggttgaggac ctcccggacg tggtgccaga ggtgcaggtc gatgtgttcg aggaagtccg 75480 ccgcccgggc ctccgcgcgg gccgcctgac ggggcgggcc gccggccgcg ccctcccatt 75540 gctggtaggt gaggtggagg cgttcgaggg cgtggccgag tacggcgggg tcgagcggca 75600 cgatgcggga aagggccccc acgtaggggg gccaccaggt ggtggcggcc tctctgagca 75660 ggacgcggag ccggccggtc ctgccgcacg cggcgacgaa gcaggccggt ggcgggcaga 75720 ggactctcag gagggcgtcc gtctgggcgg gggtcccctg ccagcggttc cggcgttcgg 75780 cgtcctccca ctggccgcgg gtgaggccga gctcggtcgc ggtctcgttg acggtgagtc 75840 cggcgacggt acggcactgg gcgagggtgc cgggctcttc gacgagatcg accggagagc 75900 accagagggc cgccgcgagg gccttcacct gggtgttgtc gggggtggcg gtgccggctt 75960 cccacgcctc gacgaggccg gggtgcgcgg ggtgtccgca gtaggcggtg acggcccagg 76020 cgacctggcc gagcgtcagg ccgagctggg cgcggacggc cgcggcacgg gtgggatcga 76080 agcggggcag ggcatacgga tcgtctgcgg gtggcatagc gggacaccgt agggaccccg 76140 cggtccacgg ccaagggccg gaacggtctc gatgtcggct ccgccgcccg gcgttcggct 76200 tcttcgtcgg atctcctgag cgggcagacc gtcgatgacc tgctctttca tgggaggagg 76260 cgggcaagcg gagagaagag gaggctgagg cgactgtcgg ttcctccaga atccgcgagg 76320 aactggcgcc ttctcttggg ggagttgacg aggttcaggc cgggccataa agtcccgtcc 76380 cgtccacaac ggaaaacttc ttccgtcatg cgaaacctgt ggtgacagcc gcccaccccc 76440 gcggctcgcc cccatcggcc atgctcccgg ttcgggccgt cccccggcac cggtcactct 76500 gcccacacgc ccccggcagt ccgctgcccg cgggcggtgt ctcaaggacc tgccttgctg 76560 ccccgcgcca ctgaccacgc atcgccgacc ccaccccatc cggtcgacga gatccttccc 76620 gcccgccgca tgctgcccgc cgccctccaa cacgtggcga gcatgtacgc cggcctgacc 76680 gcaccaccgc tgatcatcag cagcgccctg gggctgaccc cggcccagct ctccgccctc 76740 ctggccgccg cgctgctgat cgccgggctc ggcacgatcg cccagaccct cggcgtctac 76800 ggcgtcggcg ccgggttgcc cctcgtcaac ggcgtctcgt tcgccgtcgt gtcaccggcg 76860 ctcgccaccg ccgccaccca ggggcgcgac ggcgccctcc cggcgatctt cggggccacc 76920 ctcgtggcgg gactcctctg cctgctcctc gctcccgtct tctgccgact ggtcaggttc 76980 ttcccaccgg tcgtcagcgg ctgcgtcatc accctggtcg gcatctccct cctgccggtc 77040 gccggcacct gggcccgggg cggagacgcc gaagccgccg gcttcggctc ccccgccgac 77100 ctggccctgg cggcgacgac cctcgtcatc accctgaccg tgcaccgcat gctctcgggc 77160 cgcttcctcg ggcgggtcgc catcctcatc ggcatgctcg cgggcaccct gatcgcgatc 77220 ccgctgggca aggtcgacct cgaccccctc gcccaggcgc ccctcttcgc cctgcccacg 77280 cccttcggct tcggcacccc gcagttcgtc cccaccgtga tcgccaccgc cgcggtcgtg 77340 atgatcgtgt ccatgatgga gtccaccgcc gcgctgctgg cgctgggcgc ggtcgccgaa 77400 cggccggtcc gggaccggac catcgccgga agcctccgcg ccctcggcct cgccacggtc 77460 ctcggcggcg tcctcggctc gttcaccagc acgtcgtacg cgcagaacgt cggcctggtc 77520 tccctcagcc ggatccgcag ccgctatgtg gtcacgctct gcggcgccgt cctcgtcctg 77580 atgggcttcg tgcccgtcct gggctcgttc gtcgccctcg tccctctgcc cgtcctcggc 77640 ggtgcggggg tggtcttctt cggctccgtc gccgtcacgg gcatccgtac gctggccaag 77700 gccgccctcg gcaccggaca caacgctgtg atcgtctccg tcaccctcgc cttcggtctc 77760 ttccccgtcc tggacccgga cttctacgcc cgtcttcccg ccccggtggc gaccgtgctc 77820 ggctcgggga tcaccgccgg ctgcctggtc gcggtcctcc tcaactacct cctgaaccac 77880 ctgggccgcg gcaccgaggc cgaccccgac gcgatctccg cggaacaggt caccgccctc 77940 gacaccgcgg acaccgtcct cgggccgaag cgttcctccg actggacgcc cttccagccc 78000 tccggcagcc cctccggcac ccctgaccac ggccgtcaca ccaggggcac ggcacggccc 78060 gctcccgcct ggccctacgt gaccggcccc gtggacccca ccgacaccgg gcggcaccac 78120 cggccgcacg aggttccggc gccgccccac cgaccagacg aggtgccccc gccgctccac 78180 ccctctgccg ctcacgaagg cgaacccccg cccgccgtca ccgagaacgc ggtctttccc 78240 ggaccgctcc acccgctcca cccgctccac ccccggccca ccggtcgtcc cgaccgtccc 78300 cggcaacggc acagtgcgga ggccgacccc tggcagcatc cgcagacccc ctccgcatcc 78360 ggcgacagcc agtagagacg acctcccccg acctcttcgc agagcccggc atcgcacagg 78420 cccggcggag aggtggcgcc gacccacccg accaccgccg gaagcgcccc cggggacccg 78480 tgtcccacgg attccccggc gacaagacga ggtagccccg atgaccaccg tttccgccgc 78540 ccgccaccgt gcgggcggct ccccgcgcgg cggcacgtcc cgcccgggcc ccgacgagag 78600 aatcgcccag gtcgtggccg aggccctcgg atccgcccgg acggtcctcg acccggatgc 78660 gctgcccggc ctcggcacca cgcgactccc gttcggcgac gggaggttcg acgcggcgat 78720 gatgctctgc aacgcccccg gcgtccccga cgcgctctcg cggctcgggg aactgcgccg 78780 cgtgacacgg ggccccgtcg tggtcctcgc gaccgacccc tcgcgcgtcc gctcgttctg 78840 gctggaccgg tacgcccccg aggtcctggc cgtcgaagcg cggcgtcatc cgccgatcgc 78900 cgatctgacc gccgtcctcg ggggttccgc cgaggtgcgg agcgtccccg ttcccctcga 78960 ctgcaccgac accttcgacg aggcgtacta cggaagaccc gagaagctcc tggacccgtc 79020 ggcccgccag gcggggtcgg cctggagctt cgtggacgac cgggtccgcg aggagttcga 79080 cacgaccctg cgccgcgaac tccggtcggg ggagtgggac gagcgcttcg gccacctccg 79140 ccgccggccc gtctacgagg gatcactggt gatcgtccgt gccgtcccct gacgtcctcc 79200 cggggacgcg ccacccccgg ggtcgcgtca gcggtctccg gccaggtgcc ccgagagctc 79260 gcgcatcagc gtctcgtgct gctggagcag gtagaagtgg ccgccgggca ggacccgtac 79320 ccggaagccc tcgggtgcga catccgccca ggcgtccatg tcccctaccg ccacgttcgg 79380 atccgtgtcg ccgatccagg cgtgcaccgg acagccgacg gcggtgggga cgcgggggcc 79440 gtaggtgctc accacggtga agtccgcccg gaccgcgggc agcacgagct gtcggatgtc 79500 cgggtcgtca agcagggcgg tatcggtccc gccgagcccg cgcagtacgg cgaccagctc 79560 gtcgtccccc ttccggtgca ggtcgagcgg ggtcagccgg tgcggggcct tgcggctgga 79620 gacgtggagg gcggcgggcg tgacgcggtg ccgctcctcc aggcgcagcg ccacctcgta 79680 ggccagggac gcgcccatgc tgtggccgaa gagcgtcagg ggcacgtccg cgagcggcag 79740 cagtgccgcc gtgacccggt cggcgagcac gtccatccgg tcgacgaacg gctcgttgaa 79800 ccgctcctgg cgtccggggt actgcgccac caggacctcg gtgtcgccgc cgaaggcgct 79860 gccccaggcg tggaagaagc tcgcggaacc gcccgcgtgc ggcaggaccg ccagccgccg 79920 ccggggcgcg ggagtgctgg agtacctgcg gaaccacgtc gtgctgtccg tgccggtcgt 79980 catgtgtgcg tacaccccgt cctcgggttc ttggggtgcc agtgtccccg cagggcccgg 80040 tgtccggacg cggtgggggt ccggtggcga gccgcttacg tgtcccggcg cttccgggac 80100 cggcggccgc acacgtgtcg gcccccacga acaccagggt gcgtgggggc cgatgcgtgt 80160 ttcgagtcct ggtctgacga tttcaggccg aaagatatgt cggactttac agctgcgatc 80220 gaagccgatc gataatgccg tggacgggta acgtcggaat cactcggtgc tcttgagcgc 80280 accactcacg ttgacgacct cgtggcactc ccgcgcctgc tgtcccgtcg cgggcgtacc 80340 gggcttcgtg caggtcacgt cgatggtcac ggtgtccttc gcgccgatcc tgatgggagt 80400 cacccagtgg tagtcctggt tgcggaacgt ctccagcgcg atcgtggtga tcttgcggtc 80460 cccgaaggtg atcgtcatca ccccttcgtc accctggaag ttcgcgacaa cgatgtccgt 80520 gatcccgaac acggtcttct cggggaccgt gtacgtcccg gtcctggact gtcccgctcc 80580 cgacctcagg tcgatggtgg ccgagctctg ccgtcccccg ccggtcgcgg tgccgtcgcc 80640 cgtgccggcc gaaccgtcgt ccccgccgcc cgctccaccg cccgatcccg gcttctggct 80700 gctgccgccg gacggccggc ccgggccggg ggaggagccg tccgagccgc tctccgtcgg 80760 gaccgggcgg ggctgcaccg cctgggtggc cgcctcctcg gcggcgctgc gcacggccgg 80820 ccggaccagc gtgaaccagg cgatcagcag cgcgatcagc gccgcgagca gcaggagcag 80880 ccacttgggg aagaccggta tctggacgaa ctccgcgtcc agcgtcggcg ccgtgtgggg 80940 ctcctcggcg cggtcctcgg tctgctccgg ctcgccggtc tcgcgggcgt ccacggtgaa 81000 cggccagacc acggggtcgc cgaaccacac cgggctcgcg gtgcggaccc gcagccggag 81060 ttccttcgac tcgcccggct ccagcgccgg ctccgccggc gtgaaggcga accggagctc 81120 ctcgcccgcc tgcccgggcg tgaaccccac ccgtaccggg gtgttgccct ggttgcggac 81180 ggccagcaga tagcggcccc ggagccagcc gcgccggcgg cgcggcgaga ggtcggtccg 81240 cagctcgtgg aacgcgccga cgcgcaccac ggtctccagg accttgaccg actcgggctg 81300 ctcgttcggg aggatccgta caccgagggg cagctcgccg gcccgtgtct ccggcgagcg 81360 cggcggtgcc agacggagcg tcaccgtctc ggacgtgccg ggatagaggg agagccgctc 81420 gggctcgacg gtggtccatt cggcaccgtc accgacgacc ttcaggtcgt acgcctcgac 81480 gatgtcactg tcgttgcgga cggtcagggt ggtggtggcg atgtcgcccg gcgtcacgga 81540 cacggccggg atgtcgaggc cgggcgcacc gggaccggag gaggctgcgg aaggcgtcac 81600 ccgccccacc gtaggagacc tgacagatcc gtacgaggca cgcgagggca atgtccgggc 81660 agctcggctg cccggcaagc acaagtcaac tctccggtaa caatggattt ctagtctgga 81720 gagccgcctt cggcacacca ccggcccgtg gtcggctcgt gtcgtgtccg ccttcccccc 81780 accgacccag gaaaacaggt atccgatgtt ccgcaccgag gagaagaggc cggtcgcgac 81840 cggcactacg gcgcatgacg ccgtccgggg ccacccggac gcccatgccg ccggcttcgg 81900 ccgcccgcgc cgcgtcaccg tggcggtcta cgccgccgac cccgtgctgc gggtcggcgt 81960 cgtccaacag ctccgccagc gccccgagac cgagctcgtc gacgacgcgg acgcggagaa 82020 cgcgcaggtc tccctggtcg tcgtcgacgc cctcgacgac gacgtgaccg ccctgctgac 82080 ccggctgagc tacaacggcg ccacccgcgc gggactcgtg atcggcaccc tcggcgtcgg 82140 ggcgctccaa cgcgtcgtcg agtgcggggt gtcggcggtg ctgcgccgcg ccgaggccga 82200 ccaggaccag ctcgtccagc tggtcctggc ggtggccaac ggcgagggcg tgctcccggg 82260 cgacctgctc ggcgagttac tgggacacgt cggcagcctg cgccgcgcgg ccctcgaccc 82320 cggcgccctg cccctctcca ccctcaccag cagggaggcg gagatgctgc gcctggtctc 82380 ggagggcctg gacaccgcgg cgatcgcccg caagacctcg tactccgagc ggaccgtgaa 82440 gaacgtcctg cacgagatca ccacccgcct ccaactgcgc aaccgcgccc acgccgtggg 82500 ctacgcgctc cgcaacgggc tgatatgacc gtcccgtccg gaccgcggcc cggcggccgg 82560 cgcgacagcc ggagggaagg cggcgctgcc ccaaagtgca tcccgccctt cccccgggtg 82620 cggcccccgg gccctcccgc cgcgtgcgcc gccgccgcac gatgacgggg ggcacctccc 82680 ggtgccgcac cggacggaga agggcaccgt gatgaagacc gctggccccg gtggacggca 82740 ccgccggggg agactcgcct cggcgctcct gctgctcgtc cccctgctgg gcgcgacggg 82800 cgtggccggg ccggacgacc cccggaccgc ggcggccgcg gcggacgccg ccgagaccac 82860 ccgcatcgcc tacgcgggca ccggccaccg cagcctcggc gaaccggcct ccaccgactc 82920 cagcaccccg ctgttcggag cgggacccac ccactacgac accgacccgt ccgccctcgg 82980 cgaccggctg gtcttcgcga gccgccgcga cgagaagcac ccccagatct atctgcgggg 83040 cgccgacggc ggagtcctgc ggctcaccag cggcctggac gcggcccgtc cccggctcac 83100 cccggacggc gggtcggtgc tcttcgacgc cgccgacccg gccggcggct cccagcgcga 83160 cctgtggctg gtgcgcaccg acggcaccgg gctgacccgg ctgacggaca cgcccgccag 83220 cgaggaggac ccggcggtct cccccgacgg cgcccggatc gcctactcca gcgacgccga 83280 ccccctggcc gggcggcaga tctacgtccg cgccctcacg ggcggcatcc ccacccggct 83340 caccgacccg gcccgcggca cggcctccga gcccgcctgg aaccccgtcg acgacgacgt 83400 caaccgcgcg tggatcgcgt acacgtcgac cacgaccgag gacgggcgga ccaggcagcg 83460 gctgcggatc accgacggca ccaccgacga gaccctgttc accggcgcgt acgcgaactg 83520 gcagggccac ggggcggcat ggctgcccga cggggacggg atcgtgttcc tcagccccga 83580 gaccacctgc acctgcagga ccccctacga ccacgtcttc cggtcggtcg tgcacgccga 83640 ccgggaaccc tccctggtgc tcgacgagga ccgcgacgtc ctctcgccca cctggatcgg 83700 caccgccgag ggcggccacg cgatcgtcga gcgcagctcg gcggcgaccg cgcacacggc 83760 gaccctccag gacatccgcg cggacggttc cgacccgcgc gacctgcagc ggaagatcct 83820 gcgcgaggac ccccaggccg acaccaacac cgaccccgcc aaggatccgc tcttccagcc 83880 cgcgcccccg ttcgacccgt ggaccgaacg gcagaactac acccccgacg ggcgccgcct 83940 cgtcctcacc cgcttcgagg gccccgacga cgcgcggatc gagcggatct ggacggccga 84000 cgccgacggt acgaacgagg cgccgatgcc cctcgacggg cgcggcgcgc gggactggga 84060 caccgacccg acgttctccc cggacggcac ccgcctggcc ttcacccgca cctcgcccgg 84120 cggggtcggc gaggccgcgg gagacagccg catcctcctc gccgaggtcg ccaccggccg 84180 gatcaccgga gagatcgtgc ccccggccgg tgaactccgc ggcggggacg cccagccgac 84240 ctggtcctcc gacggcacca ccctggcctt cacccgcgcc cggcagatcg ccgggggcgg 84300 cggcagcaag cacgtgtgga ccgcgtccac ggctgacctg acccggcagc gcgacctgag 84360 cgcgacgcac tgcccgcgcg actgcgacgt catcgacgac agccccgcct tctcgcccga 84420 cggacgctcc ctcgccttca accgcaagaa cggcggcggg cggatcgacg agcgcaacgg 84480 actgctcctg accaccctgt ccggcgacgc ctgccaggtc ctgctgccca ccgccgcccg 84540 cggccaggac ggcgcgtgcg agcgggaact gccggacacc acgctcaccg gtccgcacca 84600 gccgcgcgac gccgcctgga ccgccgacgg caagaggctg gtcttcagct cccgggccgc 84660 ggccgcggtc aacagcccgg agaagctgaa cgtcctggac gtcggctccg gtgacatcac 84720 cccgctcacc gccgagctcg ccggacgcca gaaggaaccc accgtccagc agtccgtgga 84780 cctcgccgtc gaggcacccg ccacgacgcc cgacgtcacc gtcggcgcgt ccggcacggt 84840 caccgtccac gtggtcaacc acggtcccgc cgcctcgccc ggcacccggc tcaccgtcgt 84900 cccgccgtcc ggtgtgcgga tcaccgggat cgagtggccc ggcggcacct gcgacgccgc 84960 ctccctccag tgcgacctgg gcgtcgtcga ggccggagcc caggtccccg tggacgtcac 85020 gctcaccggc gtcaccgccg gcgacgcacc cgtcgactgg tcggtcaccg gcgccgtcct 85080 cgacccccgg cccggcgaca acgacggccg gagcgtgatc cccgtacgcg aggcaccccc 85140 gacgccgacc cccacgccga cgccgacccc cacgcccacc ccgaccccga ctccgacgcc 85200 gacccccacc cggaccccga cgcccacccc gactccgacc cggcccccgc agccccccgc 85260 gccgaaggcc ggacccgggg tgcggatcac cgtccagccc gagcccggct acgtcggcgg 85320 acgcgtcgtc gtcacgtaca gcgtccgcaa cggccgcaac gcgctcgcca ccggactccg 85380 gctcaggatc ggactgcccg ccggggtgcc ccacggcgga cttccggcgg gctgcgaccg 85440 gaacggcgcg tgcgcgctgc ccgacctcac cccgggcacg accgccgtcc tgcgggtcgt 85500 cctcagcccg aagaaggcga tgaccgcccg cgtcacggcc gtgctcgaca ccaccggcac 85560 ggacgccgac cgcagcgaca acaccgcccg ggagcggctg cgcgtcctcc agccgcgcat 85620 cgtcgccgtg cccgacatcg gcaagcccgg attcgtcacc tccgtccgag gcgtggactt 85680 cccgcccggc gtcccggtgc gcttcagctg gaaccccggg atcaccgccg ccgcctcgcc 85740 gaccttcccg gaggccgacg gcacgttcat cggacagctc ctcatcctcg ccaaggacca 85800 gaccgggccg cgcaccatca cggcctcggg ccccggattc tccccggtga agaccgactt 85860 cctggtcgtc agcggcaccg tccagccgcc ggacggggtg actcgccggt gatcc 85915 2 343 PRT Streptomyces bikiniensis 2 Met Ala Asp Val Leu Asp Ile Arg Gln Tyr Arg Ser Pro Ala Ala Thr 1 5 10 15 Ala Leu Met Ser Leu Ala Val Ala Val Leu Tyr Tyr Ala Ala Gly Arg 20 25 30 Leu Gly Leu Met Gly Arg Leu Val Val Glu Gly Val Val Val Thr Pro 35 40 45 Ile Trp Pro Pro Thr Gly Val Ala Val Ala Ala Leu Leu Leu Leu Gly 50 55 60 Ala Arg Val Trp Pro Gly Ile Ala Leu Gly Ser Phe Leu Val Ile Ala 65 70 75 80 Ser Leu Thr Thr Pro Gly Pro Thr Thr Val Val Thr Val Val Ser Asn 85 90 95 Thr Val Ala Pro Leu Cys Ala Phe Leu Leu Leu Thr Arg Ala Gly Phe 100 105 110 Arg Leu Asp Met Ala Arg Leu Arg Asp Gly Leu Ser Leu Val Phe Leu 115 120 125 Gly Gly Phe Gly Ala Met Leu Ile Ser Ala Thr Ala Gly Val Gly Leu 130 135 140 Gln Val Ala Lys Ser Ser Leu Asp Thr Thr Glu Phe Trp Pro Val Trp 145 150 155 160 Leu Ala Trp Trp Val Gly Asp Thr Met Gly Val Leu Leu Val Ala Pro 165 170 175 Leu Leu Leu Val Leu Ala Gly Pro Ala Gly Arg Phe Arg Val Arg Arg 180 185 190 Trp Lys Glu Ala Ala Leu Leu Gly Leu Ala Thr Leu Ile Leu Met Pro 195 200 205 Met Ala Val Leu Ser Pro Val Gly Met Leu Phe Leu Val Phe Pro Leu 210 215 220 Leu Ile Trp Ala Ala Leu Arg Phe Gln Leu Thr Gly Ser Met Leu Cys 225 230 235 240 Ala Leu Phe Ala Ser Val Leu Ala Thr Phe Glu Ala Asn Ala Gly Arg 245 250 255 Gly Gly Phe Leu His Leu Ser Asp Val Glu Ile Met Ala Lys Leu Gln 260 265 270 Ala Phe Asn Gly Ser Ala Ala Leu Thr Ala Leu Leu Leu Ala Ser Val 275 280 285 Ile Thr Glu Gln Arg Ala Thr Arg Arg Ser Val Arg Arg Ala Cys Arg 290 295 300 Glu Leu Ala Glu Val Leu Glu His Leu Ala Ala Gly Glu Pro Ala Pro 305 310 315 320 Gly Pro Pro Gly Thr Ala Glu Ser Arg Ala Ala Pro Ser Gly Gly Pro 325 330 335 Arg Asp Pro Phe Ser Glu Gly 340 3 279 PRT Streptomyces bikiniensis 3 Met Phe Arg Arg Arg Pro Ala Asp Ser Ser Glu Asp Leu Leu Val Arg 1 5 10 15 Leu Gly Ser Leu Thr Ala Arg Ala Arg Glu Leu Ala Glu Thr Gln Arg 20 25 30 Ser Arg Val Glu Leu Ala Val Ala Leu Gln Arg Gly Met Leu Pro Ser 35 40 45 Asp Leu Pro Ser Leu Pro Gly Ala Arg Leu Ala Val Arg Tyr Glu Pro 50 55 60 Ala Asn His Gly Leu Asn Val Gly Gly Asp Trp Tyr Asp Ala Phe Pro 65 70 75 80 Leu Pro Gly Gly Arg Ile Gly Met Ser Ile Gly Asp Val Gln Gly His 85 90 95 Asn Ile Glu Ala Ala Ala Phe Met Gly Gln Val Arg Val Ala Leu Arg 100 105 110 Ala Leu Ala Ser Val Thr Ala Asp Pro Gly Glu Leu Leu Gly Arg Thr 115 120 125 Asn Asp Leu Leu Val Ser Leu Gly Ala Asp Leu Phe Ala Thr Cys Thr 130 135 140 Phe Leu Arg Leu Asp Pro Ala Ala Gly Thr Leu Glu Cys Ala Arg Ala 145 150 155 160 Gly His Ile Pro His Ile Trp Ala Thr Ala Asp Gly Arg Ser Gly Ile 165 170 175 Asp Asp Ser Glu Gly Gly Pro Pro Leu Gly Val Leu Arg Gly Ala Asp 180 185 190 Tyr Pro Ala Thr Arg His Arg Leu Thr Ala Asp Gly Val Phe Val Leu 195 200 205 Leu Thr Asp Gly Val Val Glu Gly Pro Ser Leu His Ile Asp Glu Gly 210 215 220 Leu Asp Arg Val Thr Arg Leu Ala Gly Ile Thr Ala Val Ala Gly Leu 225 230 235 240 Asp Val Asp Ala Leu Ala Thr Ala Val Met Arg Leu Ala Ala Thr Val 245 250 255 Gly His Glu Asp Asp Ala Ala Val Leu Val Val Gly His Asp Gly Gly 260 265 270 Pro Pro Arg Pro Ala Thr Gly 275 4 293 PRT Streptomyces bikiniensis 4 Met Ala Gln Pro Gly Arg Thr Thr Phe Pro Leu Gly Gly Asp Leu Ser 1 5 10 15 Val His Arg Leu Gly Phe Gly Ala Leu Arg Leu Thr Gly Pro Gly Tyr 20 25 30 Trp Gly Pro Pro Glu Asp Arg Glu Ala Ala Ile Ser Thr Ala Arg Leu 35 40 45 Ala Val Asp Leu Gly Val Ser Phe Ile Asp Thr Ala Asp Ser Tyr Gly 50 55 60 Leu Gly Ser Asn Glu Glu Leu Leu Ala Glu Ala Leu Arg Pro Tyr Pro 65 70 75 80 Asp Gly Leu Val Ile Ala Thr Lys Ala Gly Gln Cys Arg Pro Arg Pro 85 90 95 Asp Gln Trp Val Pro Cys Gly Arg Pro Glu Tyr Leu Arg Gln Gln Ala 100 105 110 Glu Leu Ser Leu Arg Arg Leu Arg Leu Asp Arg Ile Asp Leu Phe Gln 115 120 125 Leu His Arg Ile Asp Pro Lys Val Pro Ala Ala Glu Gln Phe Gly Ala 130 135 140 Leu Gly Glu Leu Gln Asp Glu Gly Lys Ile Arg His Ile Gly Leu Ser 145 150 155 160 Lys Val Thr Val Arg Glu Val Glu Ala Ala Arg Glu His Ile Thr Val 165 170 175 Ala Ser Val Gln Asn Val Tyr Asn Leu Thr Asp Arg Arg Asn Asp Glu 180 185 190 Val Val Glu Tyr Cys Glu Lys His Glu Ile Ala Phe Ile Ala Trp Leu 195 200 205 Pro Ile Ala Arg Gly Ala Leu Ala Ala Gly Gly Ser Pro Val Ala Asp 210 215 220 Ile Ala Thr Glu Leu Glu Val Ser Ala Gly Gln Val Ala Leu Ala Trp 225 230 235 240 Leu Leu His Arg Ser Pro Ala Val Ile Pro Ile Pro Gly Thr Ser Ser 245 250 255 Pro Ala His Leu Arg Glu Asn Val Ala Ala Ser Gly Ile Ala Leu Ser 260 265 270 Asp Gly Gln Leu Ala Arg Leu Asn Ala Leu Gly Arg Thr His Asp Asp 275 280 285 Ala Thr Val Pro Val 290 5 405 PRT Streptomyces bikiniensis 5 Met Thr Met Lys Arg Asn Leu Gly Asp Leu Ala Val Phe Gly Gly Pro 1 5 10 15 Ser Ala Phe Leu Gln Pro Leu His Val Gly Arg Pro Asn Val Gly Asp 20 25 30 Arg Ala Arg Phe Leu Asp Arg Val Asn Trp Ala Leu Asp His Gln Trp 35 40 45 Leu Thr Asn Gly Gly Pro Leu Ala Arg Glu Phe Glu Gln Arg Val Ala 50 55 60 Glu Leu Ala Gly Val Arg Tyr Cys Val Ser Thr Cys Asn Ala Thr Val 65 70 75 80 Ala Leu Gln Leu Leu Ala Arg Ala Ala Asp Leu Ser Gly Glu Val Ile 85 90 95 Met Pro Ser Leu Thr Phe Pro Ala Thr Ala Gln Ala Phe Arg Trp Leu 100 105 110 Gly Leu Thr Pro Val Phe Val Asp Ile Asp Pro Ala Thr Asn Cys Leu 115 120 125 Asp Pro Asp Leu Ile Glu Ala Ala Ile Thr Pro Arg Thr Ser Ala Val 130 135 140 Val Pro Val His Leu Trp Gly Arg Pro Cys Ala Val Asp Arg Leu Ala 145 150 155 160 Lys Val Ala Ala Asp His Gly Leu Arg Leu Phe Tyr Asp Ala Ala His 165 170 175 Gly Leu Gly Cys Thr Ser Glu Gly Gln Pro Ile Gly Gly Phe Gly Gln 180 185 190 Ala Glu Val Phe Ser Phe His Ala Thr Lys Val Val Asn Ala Phe Glu 195 200 205 Gly Gly Ala Val Val Thr Asp Asp Glu Arg Leu Ala Gln Arg Val Arg 210 215 220 Ala Met His Asn Phe Gly Phe Thr Gln Gly Arg Val Ser Thr Glu Thr 225 230 235 240 Gly Thr Asn Gly Lys Met Thr Glu Ala Ala Ala Ala Met Gly Leu Thr 245 250 255 Ser Leu Asp Ala Phe Glu Glu Thr Val Arg Arg Asn Glu Ala Asn His 260 265 270 Asp Asp Tyr Arg Ser Glu Leu Ala Gly Leu Ala Gly Leu Lys Val Met 275 280 285 Glu Phe Asp Arg Ala Glu Arg Asn Asn Tyr His Tyr Leu Val Val Glu 290 295 300 Val Asp Ala Ala Val Thr Gly Val His Arg Asp Leu Leu Asp Glu Val 305 310 315 320 Leu Arg Ala Glu Asn Ile Met Cys Gln Arg Tyr Phe Ser Pro Gly Cys 325 330 335 His Glu Met Glu Pro Tyr Arg Ser Glu Arg Pro Val Ser Leu Pro His 340 345 350 Thr Glu Arg Leu Ala Arg Lys Val Leu Ala Leu Pro Thr Gly Pro Thr 355 360 365 Val Ser Arg Glu Asp Ile Arg Arg Val Cys Asp Ile Val Arg Leu Thr 370 375 380 Leu Glu Arg Gly His Glu Val Thr Arg Arg Ala Asp Glu Arg Val Pro 385 390 395 400 Ser Thr Thr Ala Pro 405 6 259 PRT Streptomyces bikiniensis 6 Met Lys Asn Val Val Ser Asn Thr Ile Tyr Gly Asp His Pro Thr Phe 1 5 10 15 Pro Val Gly Met Asn Val Leu Asp Lys Glu Leu Ala Asp Arg Met Arg 20 25 30 Pro Gly Ala Glu Gly Pro Asp Val Glu Arg Gly Thr Phe Asp Ala Asp 35 40 45 His Arg Ala Glu Gly Leu Asp Val Pro Thr Val Ala His Thr Met Ile 50 55 60 Gly Leu Gln Arg Leu Asp Asn Ile Gln Arg Cys Val Glu Arg Val Leu 65 70 75 80 Gln Asp Asp Val Pro Gly Asp Leu Ile Glu Thr Gly Val Trp Arg Gly 85 90 95 Gly Ala Cys Ile Leu Met Arg Ala Leu Leu Lys Ala His Gly Val Glu 100 105 110 Asp Arg Thr Val Trp Leu Ala Asp Ser Phe Ala Gly Val Pro Val Thr 115 120 125 Ser Glu Asp Ser His Pro Leu Asp Arg Ala Met Glu Phe His His Leu 130 135 140 Asn Trp Val Leu Ser Cys Ser Glu Glu Gln Val Arg Glu Asn Phe Ala 145 150 155 160 Arg Tyr Gly Leu Leu Asp Glu Gln Val Arg Phe Leu Pro Gly Met Phe 165 170 175 Ala Asp Thr Leu Pro Thr Ala Pro Ile Asp Arg Leu Ala Val Leu Arg 180 185 190 Val Asp Gly Asp Leu Tyr Glu Ser Thr Arg Asp Ala Leu Val Asn Leu 195 200 205 Tyr Pro Lys Leu Ser Val Gly Gly Phe Val Ile Val Asp Asp Tyr Leu 210 215 220 Ile Pro Ala Cys Lys Gln Ala Val His Asp Tyr Arg Ser Glu His Gly 225 230 235 240 Ile Asp Glu Pro Ile Glu Thr Val Asp Val Thr Gly Val Tyr Trp Arg 245 250 255 Arg Glu His 7 485 PRT Streptomyces bikiniensis 7 Met Thr Ser His Ala Ser Thr Ala Ala Asp Pro Val Ala Leu Cys Ala 1 5 10 15 Arg Pro Gly Ala Asp Leu Pro Ala Ala Val His Thr Val His Arg Ala 20 25 30 Leu Val Ser Asp Gly Arg Val Gly Val Asp Glu Gly Pro Thr Val Ala 35 40 45 Arg Arg Leu Val Arg Leu Ala Glu Arg Tyr Gly Asn His Pro Phe Thr 50 55 60 Pro Leu Glu Glu Ala Arg Arg Met Leu Asp Val Asp Arg Ala Ser Phe 65 70 75 80 Gly Arg Leu Leu Gly Leu Phe Gly Arg Val Pro Glu Leu Arg His Ala 85 90 95 Val Glu Asn Gly Pro Ala Gly Lys Tyr Trp Gln Asn Thr Leu Leu Pro 100 105 110 Leu Glu Arg Arg Gly Val Phe Asp Ala Ala Leu Ala His Lys Pro Ala 115 120 125 Phe Pro Tyr Val Val Gly Leu Tyr Pro Gly Pro Ser Cys Met Phe Arg 130 135 140 Cys His Phe Cys Val Arg Val Thr Gly Ala Arg Tyr Asp Pro Ser Ala 145 150 155 160 Leu Glu Ser Gly Asn Ala Met Phe Ala Ser Val Ile Asp Glu Ile Pro 165 170 175 Ala Gly Asn Pro Tyr Ala Met Tyr Phe Ser Gly Gly Leu Glu Pro Leu 180 185 190 Thr Asn Pro Gly Leu Gly Ala Leu Ser Ser Arg Ala Ala Ala Arg Gly 195 200 205 Leu Arg Pro Thr Val Tyr Thr Asn Ser Phe Ala Leu Thr Glu Arg Thr 210 215 220 Leu Asp Arg Gln Pro Gly Val Trp Asp Leu His Ala Val Arg Thr Ser 225 230 235 240 Leu Tyr Gly Leu Asn Asp Glu Glu Tyr Glu Glu Thr Thr Gly Lys Arg 245 250 255 Ala Ala Phe Gly Arg Val Arg Ala Asn Leu Arg Arg Phe Gln Gln Leu 260 265 270 Arg Ser Glu Arg Glu Ser Pro Ile Arg Leu Gly Leu Ser Tyr Ile Val 275 280 285 Leu Pro Gly Arg Val His Arg Leu Leu Asp Leu Val Asp Phe Ile Ala 290 295 300 Asp Leu Asn Glu Ala Ala Pro Asp Arg Pro Val Asp Phe Leu Asn Val 305 310 315 320 Arg Glu Asp Tyr Ser Gly Arg Glu Asp Gly Arg Leu Phe Glu Ala Glu 325 330 335 Arg Ala Glu Leu Gln Glu Gly Leu Leu Ala Phe Glu Glu Ala Val Ser 340 345 350 Arg Arg Thr Pro Thr Leu Asn Ile Asp Tyr Gly Tyr Ala Leu His Ser 355 360 365 Leu Lys Thr Gly Ala Asp Ala Glu Leu Leu Arg Ile Arg Pro Gly Thr 370 375 380 Met Arg Arg Ser Ala His Pro Gln Val Ser Val Gln Val Asp Leu Leu 385 390 395 400 Gly Asp Val Tyr Leu Tyr Arg Glu Ala Gly Phe Pro Asp Leu Thr Gly 405 410 415 Ala Asp Arg Tyr Val Ala Gly Arg Val Gly Pro Gly Thr Ser Leu Thr 420 425 430 Glu Val Val Glu Arg Phe Val Asp Asp Gly Arg Leu Ile Ala Pro His 435 440 445 Ala Gly Asp Glu Tyr Phe Met Asp Gly Phe Asp Gln Val Val Ala Ala 450 455 460 Arg Leu Asn Gln Leu Glu Ala Asp Val Val Ala Gly Trp Glu Asp Ala 465 470 475 480 Arg Gly Phe Leu Arg 485 8 836 PRT Streptomyces bikiniensis 8 Met Arg Thr Ala Thr Ser Ala Glu Arg Thr Ser Val Ser Met Leu Phe 1 5 10 15 Gly Thr Thr Arg Thr Gly Arg Arg Ile Arg Arg Thr Val Gly Ser Ala 20 25 30 Leu Ala Ala Leu Cys Val Gly Gly Leu Leu Thr Ala Pro Ser Ala Ala 35 40 45 Gly Ala Pro Ala Ala Glu Pro Gly Thr Ala Arg Val Arg Gly Leu Val 50 55 60 Ala Lys Met Thr Leu Asp Glu Lys Ile Ser Phe Val His Trp Thr Thr 65 70 75 80 Gly Pro Val Gly Gly Pro Thr Met Thr Gly Ile Gly Tyr Leu Pro Gly 85 90 95 Val Pro Arg Leu Gly Ile Pro Glu Leu Arg Thr Ala Asp Gly Pro Val 100 105 110 Gly Ile Arg Leu Leu Gly Gly Thr Ala Thr Ala Met Pro Thr Pro Val 115 120 125 Ala Leu Ala Ala Thr Phe Asp Glu Arg Leu Ala Glu Glu Tyr Gly Thr 130 135 140 Val Leu Gly Arg Glu Gly Arg Ala Leu Gly Gln Asp Ile Val Leu Gly 145 150 155 160 Pro Met Thr Asn Val Ile Arg Val Pro His Ala Gly Arg Asn Phe Glu 165 170 175 Thr Tyr Ser Glu Asp Pro Leu Leu Ser Ser Arg Met Ala Ala His Glu 180 185 190 Val Arg Gly Ile Gln Asn Gln Gly Leu Met Ala Thr Val Lys His Phe 195 200 205 Ala Ala Asn Asn Gln Glu Tyr Gln Arg Glu Thr Ile Asp Ala Val Val 210 215 220 Asp Glu Gln Thr Leu Gln Glu Val Glu Leu Pro Ala Phe Arg Ser Ala 225 230 235 240 Val Arg Ala Gly Ala Ala Ser Val Met Cys Ser Tyr Asn Lys Val Asn 245 250 255 Gly Ala His Ala Cys Gly Asn Glu His Leu Leu Gln Glu Val Leu Arg 260 265 270 Glu Gln Trp Asp Phe Arg Gly Trp Val Val Ser Asp Trp Leu Ala Thr 275 280 285 His Ala Thr Gly Asp Ile Thr Arg Gly Leu Asp Gln Glu Leu Gly Val 290 295 300 Glu Leu Thr Leu Gly Gln Pro Val Pro Glu Ser Lys Tyr Phe Ser Ser 305 310 315 320 Ala Leu Arg Ala Ala Val Arg Asp Gly Ser Val Pro Glu Ala Thr Leu 325 330 335 Asp Arg Ser Val Val Arg Ile Leu Gly Gln Met Glu Arg Phe Gly Leu 340 345 350 Leu Asp Gly Lys Ala Thr Glu Arg Pro Gln Arg Asp Pro Glu Ala Gly 355 360 365 Arg Ala Ala Ala Arg Thr Ile Ala Glu Asn Gly Gly Val Leu Leu Arg 370 375 380 Asn Glu Arg Arg Thr Leu Pro Leu Thr Gly Glu Asp Ala Thr Asp Ile 385 390 395 400 Ala Val Ile Gly Asn Ser Ala Lys His Pro Lys Val Thr Gly Asn Gly 405 410 415 Ser Ala His Val Ile Pro Asp Arg Ala Thr Ala Pro Val Asp Ala Leu 420 425 430 Ala Arg Arg Ala Gly Glu Lys Ala Arg Val Val His Glu Pro Gly Glu 435 440 445 Asp Leu Val Gly Val Pro Val Pro Glu Ser Ser Leu Thr Pro Ala Phe 450 455 460 Thr Ser Gly Lys Gln Leu Asp Pro Ser Gly Gln Gly Val Phe Tyr Glu 465 470 475 480 Gly Arg Leu Thr Val Pro Ala Asp Gly Asp Tyr Lys Ile Ala Phe Thr 485 490 495 Ala Val Gly Gly Val Ala Asn Leu Gln Ile Ala Gly Gln Ser Ala Val 500 505 510 Leu Gly Thr Glu Ala Phe Gly Thr Val Thr Thr Thr Met Arg Leu Thr 515 520 525 Arg Gly Thr His Ala Val Thr Met Asn Gly Trp Ala Phe Glu Gln Thr 530 535 540 Pro Leu Ser Val Glu Leu Ser Trp Val Thr Pro Glu Ala Ala Arg Asp 545 550 555 560 Asp Phe Asp Arg Ala Val Ala Ala Ala Ala Glu Ala Arg Thr Ala Val 565 570 575 Val Phe Ala His Asp Asp Ser Ala Glu Gly Val Asp Arg Ser Ser Leu 580 585 590 Ser Leu Pro Gly Arg Gln Asp Glu Leu Ile Ala Ala Ile Thr Lys Val 595 600 605 Asn Pro Arg Thr Ile Val Val Leu Asn Thr Gly Ser Ser Val Leu Met 610 615 620 Pro Trp Leu Arg Glu Thr Ala Ala Val Leu Glu Met Trp Tyr Pro Gly 625 630 635 640 Gln Glu Gly Ala Glu Ala Thr Ala Ala Leu Leu Phe Gly Asp Ala Asn 645 650 655 Pro Ser Gly Arg Leu Thr Gln Thr Phe Pro Ala Thr Glu Thr Gly His 660 665 670 Pro Met Ala Gly Asp Pro His Arg Tyr Pro Gly Val Asp Gly Lys Glu 675 680 685 Thr Tyr Ser Glu Gly Leu Asp Val Gly Tyr Arg Trp Tyr Asp Arg Thr 690 695 700 Gly Val Ala Pro Leu Phe Pro Phe Gly Tyr Gly Leu Ser Tyr Thr Thr 705 710 715 720 Phe Ala Tyr Ser Asp Leu Ser Val Ala Arg Thr Ala Arg Gly Leu Glu 725 730 735 Ala Thr Val Thr Val Arg Asn Thr Gly Asp Arg Ala Gly Arg Glu Thr 740 745 750 Val Gln Val Tyr Leu Gly Ala Ser Pro Asp Thr Gln Ala Pro Gln Ala 755 760 765 Leu Arg Lys Leu Ala Gly Phe Thr Lys Val Thr Leu Arg Pro Gly Glu 770 775 780 Gln Arg Arg Val Thr Val Pro Val Asp Glu Gln Gln Leu Arg Tyr Trp 785 790 795 800 Asp Thr Ala Ala Gly Thr Trp Lys Pro Gly Thr Gly Arg Arg Ala Val 805 810 815 His Val Gly Pro Ser Ala Ala Glu Thr Ser Leu Thr Thr Ser Val Thr 820 825 830 Val Pro Ser Arg 835 9 401 PRT Streptomyces bikiniensis 9 Met Gly Leu Pro Leu Thr Ser Thr Lys Thr Ala Pro Val Ser Tyr Pro 1 5 10 15 Phe Gly Arg Pro Glu Gly Leu Asp Leu Asp Glu Ala Tyr Glu Gln Ala 20 25 30 Arg Lys Ser Glu Gly Leu Leu Trp Val His Met Pro Tyr Gly Glu Pro 35 40 45 Gly Trp Leu Val Ser Arg Tyr Asp Asp Ala Arg Phe Val Leu Gly Asp 50 55 60 Arg Arg Phe Ser His Ala Ala Glu Ala Glu Asn Asp Ala Pro Arg Met 65 70 75 80 Arg Glu Leu Arg Thr Pro Asn Gly Ile Ile Gly Met Asp Ala Pro Asp 85 90 95 His Thr Arg Leu Arg Gly Leu Val Thr Lys Ala Phe Thr Pro Arg Arg 100 105 110 Val Glu Ala Met Arg Pro His Val Arg Arg Met Thr Ala Ser Leu Leu 115 120 125 Arg Asp Met Thr Ala Leu Gly Ser Pro Val Asp Leu Val Asp His Tyr 130 135 140 Ala Val Pro Leu Pro Val Ala Val Ile Cys Gly Leu Leu Gly Val Pro 145 150 155 160 Glu Glu Asp Arg Asp Leu Phe Arg Gly Trp Cys Glu Ile Ala Met Ser 165 170 175 Thr Ser Ser Leu Thr Ala Glu Asp His Val Arg Leu Ala Gly Glu Leu 180 185 190 Thr Gly Tyr Leu Ala Asp Leu Ile Thr Ala Arg Arg Ala Ala Pro Arg 195 200 205 Asp Asp Leu Val Ser Ala Leu Val Glu Ala Arg Asp Ala Gln Gly Arg 210 215 220 Leu Ser Gln Glu Glu Leu Val Asp Leu Ile Val Phe Leu Leu Phe Ala 225 230 235 240 Gly His Glu Thr Thr Ala Ser Gln Ile Ser Asn Phe Val Leu Val Leu 245 250 255 Leu Glu Gln Pro Asp Gln Leu Ala Leu Leu Arg Asp Arg Pro Asp Leu 260 265 270 Leu Asp Asn Ala Val Glu Glu Leu Thr Arg Phe Val Pro Leu Gly Ser 275 280 285 Gln Ala Gly Phe Pro Arg Tyr Ala Thr Glu Asp Val Glu Val Gly Gly 290 295 300 Thr Leu Val Arg Ala Gly Asp Pro Val Leu Val Gln Met Asn Ala Ala 305 310 315 320 Asn Arg Asp Ala Leu Arg Phe Arg Ser Pro Gly Val Leu Asp Ile Thr 325 330 335 Arg Asp Asp Ala Gly Arg His Leu Gly Tyr Gly His Gly Pro His His 340 345 350 Cys Leu Gly Ala Ser Leu Ala Arg Leu Glu Leu Gln Glu Ala Leu Arg 355 360 365 Thr Leu Leu Asp Glu Leu Pro Gly Leu His Leu Ala Gln Pro Val Glu 370 375 380 Trp Lys Thr Glu Met Val Val Arg Gly Pro Arg Thr Met Leu Val Gly 385 390 395 400 Trp 10 407 PRT Streptomyces bikiniensis 10 Met Thr Ser Ser Cys Pro Val His Arg Thr Arg Pro Tyr Pro Phe Ser 1 5 10 15 Pro Pro Glu Gly Ile Ala Leu Asp Pro Leu Tyr Ser Arg Leu Arg Glu 20 25 30 His Glu Pro Val Ser Arg Ile Arg Met Pro Tyr Gly Gly Glu Ala Trp 35 40 45 Leu Leu Thr Arg His Ala Asp Val Arg Ala Val Leu Gly Asp Pro Arg 50 55 60 Phe Ser Met Glu Ala Gly Ala Gly Arg Asp Val Pro Arg Pro Thr Glu 65 70 75 80 Tyr Pro Leu Pro Ala Gly Gly Leu Ile Ser Met Asp Pro Pro Gly His 85 90 95 Thr Arg Leu Arg Arg Leu Ala Gly Lys Ala Phe Thr Ala Arg Arg Val 100 105 110 Glu Glu Leu Arg Pro Arg Val Ser Arg Phe Thr Asp Glu Leu Leu Asp 115 120 125 Gly Met Val Ala Arg Asp Glu Pro Ser Gly Glu Val Met Glu Asp Leu 130 135 140 Ala Leu Pro Val Ser Ile Ser Val Ile Cys Gly Leu Leu Gly Val Ser 145 150 155 160 Tyr Asp Asp Arg His Leu Phe Arg Asp Phe Ser Glu Ala Leu Val Ser 165 170 175 Ser Ser Leu Gly Pro Ala Glu Val Gln Arg Ala Thr Glu Asp Phe Ser 180 185 190 Ala Tyr Met Ala Asp Leu Val Ala Asp Arg Arg Ala Arg Pro Thr Asp 195 200 205 Asp Phe Leu Ser Thr Met Val Gln Ala Arg Asp Glu Gly Asp Arg Leu 210 215 220 Ser Glu Ala Glu Leu Leu Met Met Gly Ser Gly Leu Leu Ile Ser Gly 225 230 235 240 Tyr Glu Thr Thr Ala Thr Gln Ile Gly Asn Phe Val Leu Leu Leu Leu 245 250 255 Asp Asp Arg Arg Leu Tyr Glu Arg Leu Val Thr Glu Pro Asp Leu Val 260 265 270 Pro Ser Ala Val Glu Glu Leu Leu Arg Phe Thr Pro Leu Ser Thr Leu 275 280 285 Asp Gly Phe Ala Arg Ile Ala Leu Glu Asp Val Glu Ile Gly Gly Thr 290 295 300 Leu Ile Arg Ala Gly Glu Ala Val Ile Thr Ser Ile Ala Ser Ala Asn 305 310 315 320 Leu Asp Asp Thr Ala Phe Pro Gly Ala Ala Ser Leu Asp Leu Ala Arg 325 330 335 Ala Gln Asn Pro His Leu Gly Phe Gly His Gly Ala His Tyr Cys Met 340 345 350 Gly Ala Pro Leu Ala Arg Leu Glu Leu Gln Val Val Leu Ser Thr Leu 355 360 365 Val Glu Arg Leu Pro Glu Leu Arg Leu Ser Val Pro Ala Ser Glu Leu 370 375 380 Arg Trp Arg Ala Gly Ser Leu Leu Arg Thr Pro Glu Ala Val Pro Val 385 390 395 400 Thr Trp Gly Gly Ser Ala Ala 405 11 282 PRT Streptomyces bikiniensis 11 Met Asn Glu Gly Pro Ala Thr Thr Ala Pro Gly Ser Thr Asn Ala Gly 1 5 10 15 Asp Leu Trp Leu Arg Arg Tyr Arg Pro Val Ala Asp Pro Ala Leu Arg 20 25 30 Leu Val Cys Leu Pro His Ala Gly Gly Ser Ala Ser Ala Phe Leu Pro 35 40 45 Phe Thr Cys Leu Leu Pro Asp Arg Val Glu Val Leu Ala Val Gln Tyr 50 55 60 Pro Gly Arg Gln Asp Arg Arg Leu Glu Pro Phe Val Asp Ser Val Asp 65 70 75 80 Ala Leu Val Thr His Val Ala Gly Ala Leu Gly Pro Trp Leu Asp Arg 85 90 95 Pro Val Ala Leu Phe Gly His Ser Leu Gly Ser Leu Val Ala Phe Glu 100 105 110 Thr Ala Arg Arg Leu Ala Glu Gln Ala Pro Glu Ser Arg Leu Ala His 115 120 125 Leu Phe Val Ser Gly Arg Val Ala Pro Thr Val Ala His Arg Thr Thr 130 135 140 Ala His Leu Leu Ser Asp Asp Arg Leu Val Ala Lys Leu Ala Glu Leu 145 150 155 160 Gln Gly Thr Asp Pro Arg Val Leu Ala Asp Glu Glu Val Leu Arg Met 165 170 175 Ala Leu Pro Ala Ile Arg Asn Asp Tyr Arg Ala Ala Ala Thr Tyr Thr 180 185 190 Trp Arg Pro Gly Ala Pro Leu Ala Cys Pro Ile Thr Val Leu Thr Gly 195 200 205 Ser Ala Asp Pro His Val Pro Thr Asp Gly Ala Leu Ala Trp His Gly 210 215 220 Leu Thr Thr Gly Glu Thr Ala Phe Arg Ser Phe Pro Gly Gly His Phe 225 230 235 240 Tyr Leu Thr Glu Gln Ala Glu Ala Val Cys Arg Thr Ile Arg Thr Ala 245 250 255 Thr Gly Leu Ala Val Gly Arg Pro His Pro Ser Ser Ser Ala Ala Ala 260 265 270 Pro Tyr Asp Arg Glu Ser Val His Asp Val 275 280 12 323 PRT Streptomyces bikiniensis 12 Met Arg Val Leu Val Thr Gly Ala Ala Gly Phe Ile Gly Ser His Phe 1 5 10 15 Val Arg Gln Leu Leu Ser Gly Ser Tyr Pro Glu Leu Ala Gly Ala His 20 25 30 Val Leu Ser Leu Asp Lys Leu Thr Tyr Ala Gly Asn Thr Glu Asn Leu 35 40 45 Ala Glu Val Ala Gly His Pro Arg His Thr Phe Leu His Gly Asp Ile 50 55 60 Cys Asp Pro Pro Thr Val Ala Gln Ala Leu Arg Gly Thr Asp Leu Val 65 70 75 80 Val His Phe Ala Ala Glu Ser His Val Asp Arg Ser Ile Thr Asp Ser 85 90 95 Ala Ala Phe Val Thr Thr Asn Val Leu Gly Thr Gln Thr Leu Leu Arg 100 105 110 Ser Ala Leu Glu Ala Gly Val Ser Arg Phe Val His Val Ser Thr Asp 115 120 125 Glu Val Tyr Gly Ser Ile Pro Glu Gly Ser Ser Thr Glu Ala Asp Pro 130 135 140 Leu Asp Pro Asn Ser Pro Tyr Ala Ala Ser Lys Ala Ser Ser Asp Leu 145 150 155 160 Leu Ala Leu Ala Phe His Arg Thr His Gly Leu Asp Val Arg Val Thr 165 170 175 Arg Cys Ser Asn Asn Tyr Gly Pro His Gln His Pro Glu Lys Val Val 180 185 190 Pro Leu Phe Val Thr His Leu Leu Glu Gly Leu Arg Leu Pro Leu Tyr 195 200 205 Gly Asp Gly Leu His Arg Arg Asp Trp Leu His Val Asp Asp His Cys 210 215 220 Arg Gly Ile Ala Met Val Ala Ala Arg Gly Arg Ala Gly Glu Val Tyr 225 230 235 240 Asn Ile Gly Gly Gly Thr Glu Leu Ser Asn Val Asp Leu Thr Arg Arg 245 250 255 Leu Leu Gly Val Phe Gly Ala Asp Trp Ser Val Val Asp Arg Val Pro 260 265 270 Asp Arg Ala Ala His Asp Arg Arg Tyr Cys Val Asp Thr Arg Lys Ile 275 280 285 Thr Glu Glu Leu Gly Trp Ala Pro Arg Val Ala Phe Asp Arg Gly Leu 290 295 300 Ala Glu Thr Val Asp Trp Tyr Arg Asp Asn Gly Thr Trp Trp Lys Ala 305 310 315 320 Leu Thr Pro 13 305 PRT Streptomyces bikiniensis 13 Val Phe Glu Thr Pro Leu Lys Arg Pro Gly Val Arg Gly Ile Ile Leu 1 5 10 15 Ala Gly Gly Ser Ala Thr Arg Leu Gln Pro Leu Thr Gly Ala Leu Ser 20 25 30 Lys Gln Gln Leu Pro Val Tyr Asp Lys Pro Met Ile Tyr Tyr Pro Leu 35 40 45 Ser Val Leu Met Leu Ala Gly Ile Gln Asp Ile Leu Ile Ile Ser Ser 50 55 60 His Gln His Val Glu Thr Phe Gln Val Met Leu Gly Asp Gly Ser Arg 65 70 75 80 Leu Gly Ile Gln Leu Asp Tyr Ala Val Gln Asp Glu Pro Arg Gly Val 85 90 95 Ala Asp Ala Phe Leu Val Gly Asp Lys His Ile Gly Asn Asp Arg Val 100 105 110 Ala Leu Ile Leu Gly Asp Asn Val Phe His Gly Pro Gly Phe Ser Thr 115 120 125 Val Leu Lys His Ser Leu Arg Arg Leu Asp Gly Cys Glu Leu Phe Gly 130 135 140 Tyr Pro Ser Lys Ser Pro Glu Arg Tyr Gly Val Ala Glu Ile Asp Glu 145 150 155 160 Gln Gly His Leu Leu Ser Leu Glu Glu Lys Pro Ser Arg Pro Arg Ser 165 170 175 Asn Leu Ala Val Thr Gly Leu Tyr Phe Tyr Asp Asn Asp Val Val Glu 180 185 190 Leu Ala Lys Asp Leu Lys Pro Ser Ala Arg Gly Glu Leu Glu Ile Thr 195 200 205 Asp Ile Asn Leu Ser Tyr Leu Glu Gln Gly Arg Ala Arg Leu Thr Gln 210 215 220 Leu Gly Arg Gly Phe Ala Trp Leu Asp Met Gly Thr His Asp Ser Leu 225 230 235 240 Leu Gln Ala Gly Gln Tyr Val Gln Leu Leu Glu Gln Arg Gln Gly Val 245 250 255 Arg Ile Ala Cys Leu Glu Glu Ile Ala Leu Arg Met Gly Phe Ile Asp 260 265 270 Ala Asp Thr Cys Tyr Arg Leu Gly Glu Glu Leu Ser Ala Ser Ser Tyr 275 280 285 Gly Asp Tyr Leu Met Glu Val Ala Ser Gly Leu Gly Ala Thr Arg Thr 290 295 300 Gly 305 14 196 PRT Streptomyces bikiniensis 14 Met His Pro Leu Ser Ile Glu Gly Ala Trp Ser Gln Glu Pro Val Ile 1 5 10 15 His Ser Asp His Arg Gly Arg Ser His Glu Trp Phe Arg Gly Glu Ser 20 25 30 Phe Arg Gln Ala Phe Gly His Asp Phe Pro Val Ala Gln Val Asn Val 35 40 45 Ala Val Ser His Arg Gly Ala Leu Arg Gly Ile His Tyr Thr Glu Ile 50 55 60 Pro Pro Gly Gln Ala Lys Tyr Ser Val Cys Val Arg Gly Ala Gly Leu 65 70 75 80 Asp Val Val Val Asp Val Arg Ile Gly Ser Pro Thr Phe Gly Arg Trp 85 90 95 Glu Ile Val Pro Met Asp Ala Glu Arg Asn Thr Ala Val Tyr Leu Thr 100 105 110 Ala Gly Leu Gly Arg Ala Phe Leu Ser Leu Thr Asp Asp Ala Thr Leu 115 120 125 Val Tyr Leu Cys Ser Ser Gly Tyr Ala Pro Ala Arg Glu His Ser Val 130 135 140 Asn Pro Leu Asp Pro Asp Leu Gly Ile Ala Trp Pro Asp Asp Ile Glu 145 150 155 160 Pro Leu Leu Ser Asp Arg Asp Glu Asn Ala Pro Thr Leu Ala Thr Ala 165 170 175 Glu Arg Leu Gly Leu Leu Pro Thr Tyr Gln Ala Trp Gln Glu Gln Gln 180 185 190 Gln Ala Gln Arg 195 15 255 PRT Streptomyces bikiniensis 15 Met Thr Val Ile Ala Ala Glu Ala Asp Leu Tyr Leu Asp Leu Leu Lys 1 5 10 15 Lys Val Val Thr Asn Met Ile Tyr Glu Asp Gln Thr Asn Val Ala Gly 20 25 30 Leu Ile Thr Ser Ser Ser Tyr Ser Ala Glu Leu Arg Ser Val Gly Glu 35 40 45 Asp Phe Pro Arg Val Ala His Ser Met Val Gly Leu Lys Arg Leu Asp 50 55 60 Asn Leu Gln Lys Cys Leu Glu Asp Val Leu Arg Asp Gly Val Pro Gly 65 70 75 80 Asp Phe Ala Glu Thr Gly Val Trp Arg Gly Gly Ala Cys Ile Phe Ala 85 90 95 Arg Gly Val Phe Arg Ala His Gly Val Arg Asp Arg Lys Val Trp Val 100 105 110 Ala Asp Ser Phe Gln Gly Phe Pro Lys Thr Thr Glu Asp Asp His Gln 115 120 125 Leu Asp Val Asp Ile Asp Leu Gly Gln Tyr Asn Asp Val Leu Ser Ile 130 135 140 Pro Val Asp Val Glu Thr Val Lys Gly Asn Phe Ala Arg Tyr Gly Leu 145 150 155 160 Leu Asp Asp Gln Val Arg Phe Leu Pro Gly Trp Phe Lys Asp Thr Met 165 170 175 Pro Thr Ala Pro Ile Glu Arg Leu Ala Val Leu Arg Leu Asp Gly Asp 180 185 190 Ser Tyr Ala Ala Thr Arg Glu Val Leu Thr Asn Leu Tyr His Lys Val 195 200 205 Ser Asp Gly Gly Tyr Val Ile Val Asp Asp Tyr Cys Ile Pro Ala Cys 210 215 220 Arg Gln Ala Val His Glu Phe Arg Asp Glu His Gly Ile Thr Asp Glu 225 230 235 240 Ile His Gln Ile Asp Arg Gln Gly Ser Tyr Trp Arg Arg Ser Ser 245 250 255 16 420 PRT Streptomyces bikiniensis 16 Met Leu Asp Val Asp His Leu Leu Pro Ile Ala Phe Arg Val Arg Lys 1 5 10 15 Ser Met Lys Ser Ser Lys Val Val His Ser Arg Pro Ala Glu Ala Gly 20 25 30 Val Ala Trp Pro Val Ala Arg Thr Cys Pro Phe Thr Leu Pro Asp Gln 35 40 45 Tyr Ala Glu Lys Arg Lys Asn Glu Pro Ile Cys Arg Ala Gln Val Trp 50 55 60 Asp Asp Ser Arg Thr Trp Leu Ile Thr Lys His Glu His Val Arg Ala 65 70 75 80 Leu Leu Ala Asp Pro Arg Val Thr Val Asp Pro Ala Lys Leu Pro Arg 85 90 95 Leu Ser Pro Ser Asp Gly Asp Gly Gly Gly Phe Arg Ser Leu Leu Thr 100 105 110 Met Asp Pro Pro Asp His Asn Ala Leu Arg Arg Met Leu Ile Ser Glu 115 120 125 Phe Ser Val His Arg Val Arg Glu Met Arg Pro Gly Ile Glu Arg Thr 130 135 140 Val His Gly Leu Leu Asp Gly Ile Leu Glu Arg Arg Gly Pro Val Asp 145 150 155 160 Leu Val Ala Glu Leu Ala Leu Pro Met Ser Thr Leu Val Ile Cys Gln 165 170 175 Leu Leu Gly Val Pro Tyr Glu Asp Arg Glu Phe Phe Gln Glu Arg Ser 180 185 190 Glu Gln Ala Thr Arg Val Gly Gly Ser Gln Glu Ser Leu Thr Ala Leu 195 200 205 Leu Glu Leu Arg Asp Tyr Leu Asp Arg Leu Val Thr Ala Lys Ile Glu 210 215 220 Thr Pro Gly Asp Asp Leu Leu Cys Arg Leu Ile Ala Ser Arg Leu His 225 230 235 240 Thr Gly Glu Met Arg His Ala Glu Ile Val Asp Asn Ala Val Leu Leu 245 250 255 Leu Ala Ala Gly His Glu Thr Ser Ala Ala Met Val Ala Leu Gly Ile 260 265 270 Leu Thr Leu Leu Arg His Pro Gly Ala Leu Ala Glu Leu Arg Gly Asp 275 280 285 Gly Thr Leu Met Pro Gln Thr Val Asp Glu Leu Leu Arg Phe His Ser 290 295 300 Ile Ala Asp Gly Leu Arg Arg Ala Val Thr Glu Asp Ile Glu Leu Gly 305 310 315 320 Gly Ile Thr Leu Arg Ala Gly Asp Gly Leu Ile Val Ser Leu Ala Ser 325 330 335 Ala Asn Arg Asp Glu Ser Ala Phe Ala Ser Pro Asp Gly Phe Asp Pro 340 345 350 His His Pro Ala Ser Arg His Val Ala Phe Gly Tyr Gly Pro His Gln 355 360 365 Cys Leu Gly Gln Asn Leu Ala Arg Leu Glu Leu Glu Val Thr Leu Gly 370 375 380 Ala Val Val Glu Arg Ile Pro Thr Leu Arg Leu Ala Gly Asp Ala Asp 385 390 395 400 Ala Leu Arg Val Lys Gln Asp Ser Thr Ile Phe Gly Leu His Glu Leu 405 410 415 Pro Val Glu Trp 420 17 73 PRT Streptomyces bikiniensis 17 Val Arg Val Thr Val Asp Gln Ser Arg Cys Leu Gly Ala Gly Gln Cys 1 5 10 15 Glu Gln Leu Ala Pro Glu Val Phe Arg Gln Asp Glu Glu Gly Leu Ser 20 25 30 Arg Val Leu Val Pro Glu Pro Asp Pro Ala Ser Trp Pro Arg Val Leu 35 40 45 Gln Thr Val Asp Leu Cys Pro Val Gln Ala Val Leu Ile Asp Glu Gly 50 55 60 Pro Gly Pro Ala Pro Gln Asp Thr Lys 65 70 18 356 PRT Streptomyces bikiniensis 18 Met Ala Ala Gly Ala Pro Asp Gly Gly Pro Leu Pro Arg Thr Gly Arg 1 5 10 15 Pro His Arg Arg Gly Pro Arg Ser Arg Ala Ala Gly His Gln Val Thr 20 25 30 Ala Asp Arg Trp Ala Gly Arg Thr Val Leu Val Thr Gly Ala Leu Gly 35 40 45 Phe Ile Gly Ser His Phe Val Arg Gln Leu Glu Ala Arg Gly Ala Glu 50 55 60 Val Leu Ala Leu Tyr Arg Thr Glu Arg Pro Gln Leu Gln Ala Glu Leu 65 70 75 80 Ala Ala Leu Asp Arg Val Arg Leu Ile Arg Thr Glu Leu Arg Asp Glu 85 90 95 Ser Asp Val Arg Gly Ala Phe Lys Tyr Leu Ala Pro Ser Ile Asp Thr 100 105 110 Val Val His Cys Ala Ala Met Asp Gly Asn Ala Gln Phe Lys Leu Glu 115 120 125 Arg Ser Ala Glu Ile Leu Asp Ser Asn Gln Arg Thr Ile Ser His Leu 130 135 140 Leu Asn Cys Val Arg Asp Phe Gly Val Gly Glu Ala Val Val Met Ser 145 150 155 160 Ser Ser Glu Leu Tyr Cys Ala Pro Pro Thr Ala Ala Ala His Glu Asp 165 170 175 Asp Asp Phe Arg Arg Ser Met Arg Tyr Thr Asp Asn Gly Tyr Val Leu 180 185 190 Ser Lys Thr Tyr Gly Glu Ile Leu Ala Arg Leu His Arg Glu Gln Phe 195 200 205 Gly Thr Asn Val Phe Leu Val Arg Pro Gly Asn Val Tyr Gly Pro Gly 210 215 220 Asp Gly Tyr Asp Pro Ser Arg Gly Arg Val Ile Pro Ser Met Leu Ala 225 230 235 240 Lys Ala Asp Ala Gly Glu Glu Ile Glu Ile Trp Gly Asp Gly Ser Gln 245 250 255 Thr Arg Ser Phe Ile His Val Thr Asp Leu Val Arg Ala Ser Leu Arg 260 265 270 Leu Leu Glu Thr Gly Lys Tyr Pro Glu Met Asn Val Ala Gly Ala Glu 275 280 285 Gln Val Ser Ile Leu Glu Leu Ala Arg Met Val Met Ala Val Leu Gly 290 295 300 Arg Pro Glu Arg Ile Arg Leu Asp Pro Gly Arg Pro Val Gly Ala Pro 305 310 315 320 Ser Arg Leu Leu Asp Leu Thr Arg Met Ser Glu Val Ile Asp Phe Glu 325 330 335 Pro Gln Pro Leu Arg Thr Gly Leu Glu Glu Thr Ala Arg Trp Phe Arg 340 345 350 His His Thr Arg 355 19 326 PRT Streptomyces Bikiniensis 19 Val Thr Ala Asp Arg Trp Ala Gly Arg Thr Val Leu Val Thr Gly Ala 1 5 10 15 Leu Gly Phe Ile Gly Ser His Phe Val Arg Gln Leu Glu Ala Arg Gly 20 25 30 Ala Glu Val Leu Ala Leu Tyr Arg Thr Glu Arg Pro Gln Leu Gln Ala 35 40 45 Glu Leu Ala Ala Leu Asp Arg Val Arg Leu Ile Arg Thr Glu Leu Arg 50 55 60 Asp Glu Ser Asp Val Arg Gly Ala Phe Lys Tyr Leu Ala Pro Ser Ile 65 70 75 80 Asp Thr Val Val His Cys Ala Ala Met Asp Gly Asn Ala Gln Phe Lys 85 90 95 Leu Glu Arg Ser Ala Glu Ile Leu Asp Ser Asn Gln Arg Thr Ile Ser 100 105 110 His Leu Leu Asn Cys Val Arg Asp Phe Gly Val Gly Glu Ala Val Val 115 120 125 Met Ser Ser Ser Glu Leu Tyr Cys Ala Pro Pro Thr Ala Ala Ala His 130 135 140 Glu Asp Asp Asp Phe Arg Arg Ser Met Arg Tyr Thr Asp Asn Gly Tyr 145 150 155 160 Val Leu Ser Lys Thr Tyr Gly Glu Ile Leu Ala Arg Leu His Arg Glu 165 170 175 Gln Phe Gly Thr Asn Val Phe Leu Val Arg Pro Gly Asn Val Tyr Gly 180 185 190 Pro Gly Asp Gly Tyr Asp Pro Ser Arg Gly Arg Val Ile Pro Ser Met 195 200 205 Leu Ala Lys Ala Asp Ala Gly Glu Glu Ile Glu Ile Trp Gly Asp Gly 210 215 220 Ser Gln Thr Arg Ser Phe Ile His Val Thr Asp Leu Val Arg Ala Ser 225 230 235 240 Leu Arg Leu Leu Glu Thr Gly Lys Tyr Pro Glu Met Asn Val Ala Gly 245 250 255 Ala Glu Gln Val Ser Ile Leu Glu Leu Ala Arg Met Val Met Ala Val 260 265 270 Leu Gly Arg Pro Glu Arg Ile Arg Leu Asp Pro Gly Arg Pro Val Gly 275 280 285 Ala Pro Ser Arg Leu Leu Asp Leu Thr Arg Met Ser Glu Val Ile Asp 290 295 300 Phe Glu Pro Gln Pro Leu Arg Thr Gly Leu Glu Glu Thr Ala Arg Trp 305 310 315 320 Phe Arg His His Thr Arg 325 20 403 PRT Streptomyces bikiniensis 20 Val Val Thr His Ala Pro Asn Ser Leu Ile Ser Asp Ile Ile Arg Ala 1 5 10 15 Ser Gly Gly His Asp Ala Asp Leu Lys Asp Leu Ala Ala Arg His Asp 20 25 30 Pro Ala Asp Ile Val Arg Val Leu Leu Asp Glu Ile Thr Ser Arg Cys 35 40 45 Pro Ala Pro Val Asn Asp Val Pro Val Leu Val Glu Leu Ala Val Arg 50 55 60 Ala Gly Asp Arg Leu Phe Pro Thr Tyr Leu Tyr Val Leu Lys Gly Gly 65 70 75 80 Pro Val Arg Leu Ala Ala Lys Asp Glu Ala Phe Val Ala Met Arg Val 85 90 95 Glu Tyr Glu Leu Gly Glu Leu Ala Arg Glu Leu Phe Gly Pro Val Arg 100 105 110 Glu Asn Val Thr Gly Val Arg Gly Thr Thr Leu Phe Pro Tyr Val Gly 115 120 125 Asp Thr Ala Ser Glu Gly Glu Glu Asp Ser Gly Ala Glu His Ile Gly 130 135 140 Thr His Phe Leu Ala Ala Gln Gln Gly Ser Gln Thr Val Leu Ala Gly 145 150 155 160 Cys His Ser His Lys Pro Asp Leu Ser Glu Leu Ser Ser Arg Tyr Leu 165 170 175 Thr Pro Lys Trp Gly Ser Leu His Trp Phe Thr Pro His Tyr Asp Arg 180 185 190 His Phe Arg Ser Tyr Arg Asp Gln Pro Val Arg Val Leu Glu Ile Gly 195 200 205 Ile Gly Gly Tyr Lys His Pro Glu Trp Gly Gly Gly Ser Leu Arg Met 210 215 220 Trp Lys His Phe Phe His Arg Gly Glu Ile Tyr Gly Leu Asp Ile Val 225 230 235 240 Asp Lys Ser His Phe Asp Ala Pro Arg Ile Thr Thr Leu Arg Gly Asp 245 250 255 Gln Ser Asp Pro Asp His Leu Arg Ser Ile Ala Glu Lys Tyr Gly Pro 260 265 270 Phe Asp Ile Val Ile Asp Asp Gly Ser His Ile Asn Asp His Ile Arg 275 280 285 Thr Ser Phe Gln Ala Leu Phe Pro His Val Arg Pro Gly Gly Leu Tyr 290 295 300 Val Ile Glu Asp Leu Trp Thr Ala Tyr Trp Ser Gly Phe Gly Gly Asp 305 310 315 320 Glu Asp Pro Lys Arg Tyr Ser Gly Thr Ser Leu Gly Leu Leu Lys Ser 325 330 335 Leu Val Asp Ser Ile Gln His Glu Glu Leu Pro Glu Ala Gly Asp His 340 345 350 Arg Pro Ser Tyr Ala Asp Gln His Val Val Gly Met His Leu Tyr His 355 360 365 Asn Leu Ala Phe Ile Glu Lys Gly Thr Asn Ala Glu Gly Gly Ile Pro 370 375 380 Pro Trp Ile Pro Arg Asp Phe Glu Thr Leu Val Ala Val Ser Ser Gly 385 390 395 400 Gly His Ala 21 418 PRT Streptomyces bikiniensis 21 Met Arg Val Thr Leu Leu Ser Val Gly Ser Arg Gly Asp Val Gln Pro 1 5 10 15 Phe Val Ala Leu Gly Ile Gly Leu Lys Ala Arg Gly His Asp Val Thr 20 25 30 Leu Ala Ala Pro Ala Thr Leu Arg Pro Leu Val Glu Arg Ala Gly Leu 35 40 45 Thr Tyr Arg Leu Ser Pro Gly Asp Pro Asp Gly Phe Phe Thr Met Pro 50 55 60 Glu Val Val Glu Ala Leu Arg Arg Gly Pro Ser Phe Lys Asn Met Leu 65 70 75 80 Ala Gly Met Pro Glu Ala Pro Glu Ser Tyr Thr Gln Gln Val Val Asp 85 90 95 Ala Ile His Asp Ala Ala Glu Gly Ala Asp Leu Ile Val Asn Ala Pro 100 105 110 Leu Thr Leu Ala Ala Ala Tyr Gly His Pro Pro Ala Pro Trp Ala Ser 115 120 125 Val Ser Trp Trp Pro Asn Ser Met Thr Ser Ala Phe Pro Ala Val Glu 130 135 140 Ser Gly Gln Arg His Leu Gly Pro Leu Thr Ser Leu Tyr Asn Arg Tyr 145 150 155 160 Thr His Arg Arg Ala Ala Arg Asp Glu Trp Glu Trp Arg Arg Pro Glu 165 170 175 Ile Asp Gly Tyr Arg Arg Arg Leu Gly Leu Arg Pro Phe Gly Asp Glu 180 185 190 Ser Pro Phe Leu Arg Leu Gly His Asp Arg Pro Tyr Leu Phe Pro Phe 195 200 205 Ser Pro Ser Val Leu Pro Lys Pro Arg Asp Trp Pro Arg Gln Ser His 210 215 220 Val Thr Gly Tyr Trp Phe Trp Asp Gln His Gly Glu Pro Pro Ala Glu 225 230 235 240 Leu Glu Ser Phe Leu Glu Asp Gly Glu Pro Pro Val Ala Leu Thr Phe 245 250 255 Gly Ser Thr Trp Ser Leu His Arg Gln Glu Glu Ala Leu Gln Ala Ala 260 265 270 Leu Asp Ala Val Arg Gly Val Gly Arg Arg Leu Val Met Val Asp Gly 275 280 285 Pro Asp Ser Asp Leu Pro Asp Asp Val Leu Arg Leu His Gln Val Asp 290 295 300 Tyr Ala Thr Leu Phe Pro Arg Met Ala Ala Val Ile His His Gly Gly 305 310 315 320 Ala Gly Thr Thr Ala Glu Val Leu Arg Ala Gly Val Pro Gln Val Ile 325 330 335 Val Pro Val Phe Ala Asp His Pro Phe Trp Ala Ala Arg Leu Ser Arg 340 345 350 Thr Gly Val Ala Ala Arg Pro Val Pro Phe Ala Arg Phe Ser Arg Glu 355 360 365 Ala Leu Ala Gln Ser Val Arg Gln Ala Val Thr Asp Pro Ala Met Ala 370 375 380 Gly Arg Ala Arg Arg Leu Gly Glu Arg Val Ser Lys Glu Arg Gly Val 385 390 395 400 Asp Thr Ala Cys Asp Ile Leu Glu Lys Trp Ala Glu Thr Ala Arg Ala 405 410 415 Thr Ala 22 280 PRT Streptomyces bikiniensis 22 Met Leu Asn Arg Ile Val Arg Tyr Leu Ala Cys Pro His Cys Gly Ala 1 5 10 15 Ser Leu Ala Gln Gly Asp Arg Ala Leu Phe Cys Pro Ala Gly His Ser 20 25 30 Phe Asp Ile Ala Lys Gln Gly Tyr Val Asn Leu Leu Pro Arg Ala Thr 35 40 45 Lys Leu Arg Ala Asp Thr Lys Glu Met Val Glu Ala Arg Asp Ala Phe 50 55 60 Leu Ser Ala Gly His Tyr Asp Pro Val Met Asp Ala Leu Val Asp Leu 65 70 75 80 Ala Arg Arg Thr Ala Asp Pro Ala Val Pro Gly Cys Val Val Asp Ile 85 90 95 Gly Gly Gly Thr Gly His Tyr His Ala Gly Val Met Glu Ala Phe Pro 100 105 110 Asp Ala Gln Gly Leu Leu Leu Asp Ile Ser Lys Tyr Ala Val Arg Arg 115 120 125 Ala Ala Lys Ala His Pro Arg Ile Ala Ala Ala Val Thr Asp Ala Trp 130 135 140 Gln Thr Leu Pro Leu Arg Asp Ala Ala Ala Gly Met Val Ile Asn Thr 145 150 155 160 Phe Ala Pro Arg Asn Gly Pro Glu Leu His Arg Val Leu His Pro Arg 165 170 175 Gly Val Leu Leu Val Val Thr Pro Leu Pro Asp His Leu Arg Glu Val 180 185 190 Ile Gly Ala Leu Gly Leu Leu Gln Val Asp Glu Gly Lys Glu Ser Arg 195 200 205 Leu Ala Glu Gln Leu Ala Pro His Phe Ser Ala Val Ala Thr Glu Glu 210 215 220 Leu Thr Arg Thr Met Ala Leu Asp His Gln Ala Leu Ala His Leu Val 225 230 235 240 Gly Met Gly Pro Asn Ala Trp His Arg Asp Ala Gln Arg Asp Leu Glu 245 250 255 Thr Ile Gln Arg Leu Pro Ala Pro Thr Arg Val Thr Leu Ser Val Arg 260 265 270 Leu Ser Ala Tyr Arg Leu Ser Ala 275 280 23 4441 PRT Streptomyces bikiniensis 23 Met Arg Ala Pro Tyr Gly Asn Arg Gln Val Asn Arg Arg Phe Leu Arg 1 5 10 15 Glu Phe Arg Ala Lys Arg Pro His Cys Val Ser Pro Leu His Phe Leu 20 25 30 Ala Glu Phe Ser Glu Ser Arg Gln Thr Thr Gly Ser Ala Gly Val Thr 35 40 45 Ala Pro Ile Asp Arg Pro Gly Val Ser Met Ala Pro Lys Ser Gly Ala 50 55 60 Gln Arg Ser Ser Asp Ile Ala Val Val Gly Met Ser Cys Arg Leu Pro 65 70 75 80 Gly Ala Pro Gly Ile Asp Glu Phe Trp His Leu Leu Thr Thr Gly Gly 85 90 95 Ser Ala Ile Glu Arg Arg Ala Asp Gly Thr Trp Arg Gly Ser Leu Asp 100 105 110 Gly Ala Ala Asp Phe Asp Ala Ala Phe Phe Asp Met Thr Pro Arg Gln 115 120 125 Ala Ala Ala Ala Asp Pro Gln Gln Arg Leu Met Leu Glu Leu Gly Trp 130 135 140 Thr Ala Leu Glu Asn Ala Gly Ile Val Pro Gly Ser Leu Ala Gly Thr 145 150 155 160 Asp Thr Gly Val Phe Val Gly Ile Ala Ala Asp Asp Tyr Ala Ala Leu 165 170 175 Leu His Arg Ser Ala Thr Pro Val Ser Gly His Thr Ala Thr Gly Leu 180 185 190 Ser Arg Gly Met Ala Ala Asn Arg Leu Ser Tyr Leu Leu Gly Leu Arg 195 200 205 Gly Pro Ser Leu Ala Val Asp Ser Ala Gln Ser Ser Ser Leu Val Ala 210 215 220 Val His Leu Ala Cys Glu Ser Leu Arg Arg Gly Glu Ser Asp Leu Ala 225 230 235 240 Ile Val Gly Gly Val Ser Leu Ile Leu Ala Glu Asp Ser Thr Ala Gly 245 250 255 Met Glu Leu Met Gly Ala Leu Ser Pro Asp Gly Arg Cys His Thr Phe 260 265 270 Asp Ala Arg Ala Asn Gly Tyr Val Arg Gly Glu Gly Gly Ala Cys Val 275 280 285 Val Leu Lys Pro Leu Glu Arg Ala Leu Ala Asp Gly Asp Arg Val His 290 295 300 Cys Val Val Arg Gly Ser Ala Val Asn Asn Asp Gly Gly Gly Ser Thr 305 310 315 320 Leu Thr Thr Pro His Arg Glu Ala Gln Ala Ala Val Leu Arg Ala Ala 325 330 335 Tyr Glu Arg Ala Gly Val Gly Pro Asp Gln Val Ser Tyr Val Glu Leu 340 345 350 His Gly Thr Gly Thr Pro Val Gly Asp Pro Val Glu Ala Ala Ala Leu 355 360 365 Gly Ala Val Leu Gly Thr Ala His Gly Arg Asn Ala Pro Leu Ser Val 370 375 380 Gly Ser Val Lys Thr Asn Val Gly His Leu Glu Ala Ala Ala Gly Leu 385 390 395 400 Val Gly Phe Val Lys Ala Ala Leu Cys Val Arg Glu Gly Val Val Pro 405 410 415 Pro Ser Leu Asn His Ala Thr Pro Asn Pro Ala Ile Pro Met Asp Arg 420 425 430 Leu Asn Leu Arg Val Pro Thr Arg Leu Glu Pro Trp Pro His Pro Asp 435 440 445 Asp Arg Ala Thr Gly Arg Leu Arg Leu Ala Gly Val Ser Ser Phe Gly 450 455 460 Met Gly Gly Thr Asn Ala His Val Val Val Glu Glu Ala Pro Leu Pro 465 470 475 480 Glu Ala Gly Glu Pro Val Gly Ala Gly Val Pro Leu Ala Val Val Pro 485 490 495 Val Val Val Ser Gly Arg Ser Ala Gly Ala Val Ala Glu Leu Ala Ser 500 505 510 Arg Leu Asn Glu Ser Val Arg Ser Asp Arg Leu Val Asp Val Gly Leu 515 520 525 Ser Ser Val Val Ser Arg Ser Val Phe Glu His Arg Ser Val Val Leu 530 535 540 Ala Gly Asp Ser Ala Glu Leu Ser Ala Gly Leu Asp Ala Leu Ala Ala 545 550 555 560 Asp Gly Val Ser Pro Val Leu Val Ser Gly Val Ala Ser Val Gly Gly 565 570 575 Gly Arg Ser Val Phe Val Phe Pro Gly Ala Gly Val Lys Trp Ala Gly 580 585 590 Met Ala Leu Gly Leu Trp Ala Glu Ser Ala Val Phe Ala Glu Ser Met 595 600 605 Ala Arg Cys Glu Ala Ala Phe Ala Gly Leu Val Glu Trp Arg Leu Ala 610 615 620 Asp Val Leu Gly Asp Gly Ala Ala Leu Glu Arg Glu Asp Val Val Gln 625 630 635 640 Pro Ala Ser Phe Ala Val Met Val Ser Leu Ala Ala Leu Trp Arg Ser 645 650 655 Leu Gly Val Val Pro Asp Ala Val Val Gly His Ser Gln Gly Glu Ile 660 665 670 Ala Ala Ala Val Val Ala Gly Gly Leu Ser Leu Glu Asp Gly Ala Arg 675 680 685 Val Val Val Leu Arg Ala Arg Val Ala Glu Glu Val Leu Ser Gly Gly 690 695 700 Gly Ile Ala Ser Val Arg Leu Ser Arg Ala Glu Val Glu Glu Arg Leu 705 710 715 720 Ala Gly Gly Gly Gly Gly Leu Ser Val Ala Val Val Asn Ala Pro Ser 725 730 735 Ser Thr Val Val Ala Gly Glu Leu Gly Asp Leu Asp Arg Phe Val Ala 740 745 750 Ala Cys Glu Ala Glu Gly Val Arg Ala Arg Arg Leu Glu Phe Gly Tyr 755 760 765 Ala Ser His Ser Arg Phe Val Glu Pro Val Arg Glu Arg Leu Leu Glu 770 775 780 Gly Leu Ala Asp Val Arg Pro Val Arg Gly Arg Ile Pro Phe Tyr Ser 785 790 795 800 Thr Val Glu Ala Ala Glu Phe Asp Thr Ala Gly Leu Asp Ala Glu Tyr 805 810 815 Trp Phe Gly Asn Leu Arg Arg Pro Val Arg Phe Gln Glu Thr Val Glu 820 825 830 Arg Leu Leu Ala Asp Gly Phe Arg Val Phe Val Glu Cys Gly Ala His 835 840 845 Pro Val Leu Thr Gly Ala Val Gln Glu Thr Ala Glu Thr Ala Gly Arg 850 855 860 Glu Ile Cys Ser Val Gly Ser Leu Arg Arg Asp Glu Gly Gly Leu Arg 865 870 875 880 Arg Phe Leu Thr Ser Ala Ala Glu Ala Phe Val Gln Gly Val Glu Val 885 890 895 Ser Trp Pro Val Leu Phe Asp Gly Thr Gly Ala Arg Thr Val Asp Leu 900 905 910 Pro Thr Tyr Pro Phe Gln Arg Arg His His Trp Ala Pro Asp Gly Ser 915 920 925 Ala Ser Ala Ala Pro Thr Arg Asp Ile Arg Pro Asp Glu Thr Ala Ala 930 935 940 Val Pro Ala Asp Thr Met Asp Leu Ala Gly Gln Leu Arg Ala Asp Val 945 950 955 960 Ala Ser Leu Pro Thr Thr Glu Gln Ile Ala Arg Leu Leu Asp Gln Val 965 970 975 Arg Asp Gly Val Ala Thr Val Leu Gly Leu Asp Ala Arg Asp Glu Val 980 985 990 Arg Ala Glu Ala Thr Phe Lys Glu Leu Gly Val Glu Ser Leu Thr Gly 995 1000 1005 Val Glu Leu Lys Asn His Leu Arg Ala Arg Thr Gly Leu His Val Pro 1010 1015 1020 Thr Ser Leu Ile Tyr Asp Cys Pro Thr Pro Leu Ala Ala Ala His Tyr 1025 1030 1035 1040 Leu Arg Asp Glu Leu Leu Gly Arg Pro Ala Glu Gln Ala Val Val Pro 1045 1050 1055 Ala Gly Ile Pro Val Asp Glu Pro Ile Ala Ile Val Gly Met Gly Cys 1060 1065 1070 Arg Leu Pro Gly Gly Val Ser Ser Pro Glu Gly Leu Trp Asp Leu Val 1075 1080 1085 Ala Ser Gly Val Asp Ala Val Ser Pro Phe Pro Thr Asp Arg Gly Trp 1090 1095 1100 Asp Val Gly Gly Leu Phe Asp Pro Glu Pro Gly Val Pro Gly Arg Ser 1105 1110 1115 1120 Tyr Val Arg Glu Gly Gly Phe Leu His Glu Ala Gly Glu Phe Asp Ala 1125 1130 1135 Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln 1140 1145 1150 Gln Arg Leu Leu Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala Gly 1155 1160 1165 Ile Asp Pro His Thr Leu Arg Gly Ser Arg Thr Gly Val Tyr Ala Gly 1170 1175 1180 Val Met Ala Gln Glu Tyr Gly Pro Arg Leu His Glu Gly Ala Asp Gly 1185 1190 1195 1200 Tyr Glu Gly Tyr Leu Leu Thr Gly Ser Ser Ser Ser Val Ala Ser Gly 1205 1210 1215 Arg Ile Ser Tyr Val Leu Gly Leu Glu Gly Pro Ala Val Thr Val Asp 1220 1225 1230 Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Val Arg Ala 1235 1240 1245 Leu Arg Ser Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly Ala Thr Val 1250 1255 1260 Met Ala Glu Pro Gly Met Phe Val Glu Phe Ser Arg Gln Arg Gly Leu 1265 1270 1275 1280 Ser Ala His Gly Arg Cys Lys Ala Tyr Ser Asp Ser Ala Asp Gly Thr 1285 1290 1295 Gly Trp Ala Glu Gly Ala Gly Val Leu Leu Val Glu Arg Leu Ser Asp 1300 1305 1310 Ala Val Arg His Gly Arg Arg Val Leu Ala Val Val Arg Gly Ser Ala 1315 1320 1325 Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly Arg 1330 1335 1340 Ser Gln Ser Arg Leu Ile Arg Gln Ala Leu Ala Asp Ala Arg Leu Gly 1345 1350 1355 1360 Val Ala Asp Val Asp Val Val Glu Gly His Gly Thr Gly Thr Arg Leu 1365 1370 1375 Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Arg 1380 1385 1390 Asp Ala Gly Arg Pro Leu Arg Leu Gly Ser Leu Lys Ser Asn Val Gly 1395 1400 1405 His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met 1410 1415 1420 Ala Met Arg His Gly Val Leu Pro Lys Thr Leu His Val Asp Glu Pro 1425 1430 1435 1440 Thr Ala Glu Val Asp Trp Ser Ala Gly Ala Val Ser Leu Leu Arg Glu 1445 1450 1455 Gln Glu Ala Trp Pro Arg Gly Glu Arg Val Arg Arg Ala Gly Val Ser 1460 1465 1470 Ser Phe Gly Val Ser Gly Thr Asn Ala His Val Val Val Glu Glu Ala 1475 1480 1485 Pro Val Pro Glu Asp Gly Glu Ala Ile Glu Gly Gly Ala Pro Leu Ala 1490 1495 1500 Val Val Pro Val Val Val Ser Gly Arg Ser Ala Gly Ala Val Ala Glu 1505 1510 1515 1520 Leu Ala Gly Arg Val Ser Glu Val Ala Gly Ser Gly Arg Leu Val Asp 1525 1530 1535 Val Gly Leu Ser Ser Val Val Ser Arg Ser Val Phe Glu His Arg Ser 1540 1545 1550 Val Val Leu Ala Gly Asp Ser Ala Glu Leu Asn Ala Gly Leu Asp Ala 1555 1560 1565 Leu Ala Ala Asp Gly Val Ser Pro Val Leu Val Ser Gly Val Ala Ser 1570 1575 1580 Gly Glu Gly Gly Arg Ser Val Phe Val Phe Pro Gly Gln Gly Thr Gln 1585 1590 1595 1600 Trp Ala Gly Met Ala Leu Gly Leu Trp Ala Glu Ser Ala Val Phe Ala 1605 1610 1615 Glu Ser Met Ala Arg Cys Glu Ala Ala Phe Ala Gly Leu Val Glu Trp 1620 1625 1630 Arg Leu Ala Asp Val Leu Gly Asp Gly Ser Ala Leu Glu Arg Val Asp 1635 1640 1645 Val Val Gln Pro Ala Ser Phe Ala Val Met Val Ser Leu Ala Glu Leu 1650 1655 1660 Trp Arg Ser Leu Gly Val Val Pro Asp Ala Val Val Gly His Ser Gln 1665 1670 1675 1680 Gly Glu Ile Ala Ala Ala Val Val Ala Gly Gly Leu Ser Leu Glu Asp 1685 1690 1695 Gly Ala Arg Val Val Val Leu Arg Ala Arg Leu Ile Gly Arg Glu Leu 1700 1705 1710 Ala Gly Arg Gly Gly Met Ala Ser Val Ala Leu Pro Val Ala Val Val 1715 1720 1725 Glu Glu Arg Leu Ala Gly Trp Ala Gly Arg Leu Gly Val Ala Val Val 1730 1735 1740 Asn Gly Pro Ser Ala Thr Val Val Ala Gly Asp Val Asp Ala Val Gly 1745 1750 1755 1760 Glu Phe Val Thr Ala Cys Glu Val Glu Gly Val Arg Ala Arg Val Leu 1765 1770 1775 Pro Val Asp Tyr Ala Ser His Ser Ala His Val Glu Asp Leu Lys Ala 1780 1785 1790 Glu Leu Glu Gln Ile Leu Ala Gly Ile Gly Pro Val Thr Gly Gly Ile 1795 1800 1805 Pro Phe Tyr Ser Thr Ser Glu Ala Ala Gln Ile Asp Thr Ala Gly Leu 1810 1815 1820 Asp Ala Gly Tyr Trp Phe Gly Asn Leu Arg Arg Pro Val Arg Phe Gln 1825 1830 1835 1840 Glu Thr Val Glu Arg Leu Leu Ala Asp Gly Phe Arg Val Phe Val Glu 1845 1850 1855 Cys Gly Ala His Pro Val Leu Thr Gly Ala Val Gln Glu Thr Ala Glu 1860 1865 1870 Ser Thr Gly Arg Gln Val Cys Ala Val Gly Ser Leu Arg Arg Asp Glu 1875 1880 1885 Gly Gly Leu Arg Arg Phe Leu Thr Ser Ala Ala Glu Ala Phe Val Gln 1890 1895 1900 Gly Val Gly Val Ser Trp Pro Ala Leu Phe Asp Gly Thr Gly Ala Arg 1905 1910 1915 1920 Thr Val Asp Leu Pro Thr Tyr Pro Phe Gln Arg Arg Arg Tyr Trp Leu 1925 1930 1935 Glu Ser Arg Pro Pro Ala Ala Val Val Pro Ser Gly Val Gln Asp Gly 1940 1945 1950 Leu Ser Tyr Glu Val Val Trp Lys Ser Leu Pro Val Arg Glu Ser Ser 1955 1960 1965 Arg Leu Asp Gly Arg Trp Leu Leu Val Val Pro Glu Thr Leu Asp Ala 1970 1975 1980 Asp Gly Thr Arg Ile Ala His Asp Leu Gln His Ala Leu Thr Thr His 1985 1990 1995 2000 Gly Ala Thr Val Ser Arg Val Ser Val Asp Val Thr Thr Ile Asp Arg 2005 2010 2015 Ala Asp Leu Ser Ala Arg Leu Thr Thr Ser Ala Ala Glu Asp Gln Glu 2020 2025 2030 Pro Leu Gly Arg Val Val Ser Leu Leu Gly Trp Ala Glu Gly Val Arg 2035 2040 2045 Ala His Gly Pro Asn Val Pro Thr Ser Val Ala Ala Ser Leu Ala Leu 2050 2055 2060 Val Gln Ala Val Gly Asp Ala Gly Phe Gly Val Pro Val Trp Ala Val 2065 2070 2075 2080 Thr Arg Gly Ala Val Ser Val Val Pro Gly Glu Val Pro Glu Thr Ala 2085 2090 2095 Gly Ala Gln Leu Trp Ala Leu Gly Arg Val Ala Gly Leu Glu Leu Pro 2100 2105 2110 Asp Arg Trp Gly Gly Leu Ile Asp Leu Pro Ala Asp Ala Asp Ala Arg 2115 2120 2125 Thr Ala Gly Leu Ala Val Arg Ala Leu Ala Ala Gly Ile Ala Asp Gly 2130 2135 2140 Glu Asp Gln Val Ala Val Arg Pro Ser Gly Ala Tyr Gly Arg Arg Val 2145 2150 2155 2160 Val Gln Ala Ala His Arg Glu Pro Ser Gly Ala Lys Thr Glu Trp Arg 2165 2170 2175 Pro Arg Gly Thr Val Leu Val Thr Gly Gly Met Gly Ala Ile Gly Thr 2180 2185 2190 Arg Val Ala Arg Trp Leu Ala Arg Asn Gly Ala Glu His Leu Val Leu 2195 2200 2205 Thr Gly Arg Arg Gly Ala Gly Thr Pro Gly Ala Asp Glu Leu Ala Gly 2210 2215 2220 Glu Leu Arg Ala Ser Gly Val Gln Val Thr Leu Ala Ala Cys Asp Val 2225 2230 2235 2240 Ser Asp Arg Ala Ala Leu Ala Ala Leu Leu Asp Ala His Pro Pro Thr 2245 2250 2255 Ala Val Phe His Thr Ala Gly Val Leu Asn Asp Gly Thr Val Asp Thr 2260 2265 2270 Leu Thr Pro Ala His Leu Asp Gly Val Leu Ser Pro Lys Ala Thr Ala 2275 2280 2285 Ala Val His Leu His Glu Leu Thr Ala His Leu Asp Leu Asp Ala Phe 2290 2295 2300 Val Leu Phe Ala Ser Val Thr Gly Val Trp Gly Asn Gly Gly Gln Ala 2305 2310 2315 2320 Gly Tyr Ala Met Ala Asn Ala Ala Leu Asp Ala Leu Ala Glu Gln Arg 2325 2330 2335 Arg Ala Gly Gly Leu Ala Ala Thr Ser Ile Ser Trp Gly Leu Trp Gly 2340 2345 2350 Gly Gly Gly Met Ala Glu Gly Asp Gly Glu Val Ser Leu Asn Arg Arg 2355 2360 2365 Gly Ile Arg Ala Leu Glu Pro Ala Thr Gly Ile Glu Ala Leu Gln Arg 2370 2375 2380 Thr Leu Asp Gln Gly Ala Thr Cys Arg Thr Val Val Asp Val Asp Trp 2385 2390 2395 2400 Gly Gln Phe Ala Pro Arg Thr Ala Ala Leu Arg Arg Gly Arg Leu Phe 2405 2410 2415 Ala Asp Leu Pro Glu Val Arg Arg Val Leu Glu Ser Glu Gly Val Ala 2420 2425 2430 Arg Glu Asp Ala Gly Thr Val Glu Pro Gly Ala Val Leu Ala Glu Arg 2435 2440 2445 Leu Ala Ser Arg Ser Glu Ala Glu Gln Arg Arg Met Leu Val Glu Leu 2450 2455 2460 Val Arg Ala Glu Ala Ala Ala Val Leu Arg His Asp Thr Thr Asp Leu 2465 2470 2475 2480 Leu Ala Pro Arg Arg Ser Phe Lys Asp Ala Gly Phe Asp Ser Leu Thr 2485 2490 2495 Ala Leu Glu Leu Arg Asn Arg Leu Asn Thr Ala Thr Gly Val Val Leu 2500 2505 2510 Pro Val Thr Val Val Phe Asp His Pro Asn Pro Gly Ala Leu Ala Asp 2515 2520 2525 Phe Leu Tyr Gly Glu Ala Leu Gly Leu Ser Ala Ala Arg Ser Ser Ala 2530 2535 2540 Ser Asp Thr Ala Asp Thr Thr Arg Pro Ala Ala Ala Pro Glu Glu Pro 2545 2550 2555 2560 Ile Ala Ile Val Gly Met Ala Cys Arg Tyr Pro Gly Glu Ala Arg Ser 2565 2570 2575 Pro Glu Glu Leu Trp Lys Leu Leu Ile Asp Glu Arg Asp Val Ile Gly 2580 2585 2590 Pro Met Pro Thr Asp Arg Gly Trp Asp Val Gly Gly Leu Phe Asp Pro 2595 2600 2605 Glu Pro Gly Val Pro Gly Arg Ser Tyr Val Arg Glu Gly Gly Phe Leu 2610 2615 2620 His Glu Ala Gly Glu Phe Asp Ala Gly Phe Phe Gly Ile Ser Pro Arg 2625 2630 2635 2640 Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Thr Ser 2645 2650 2655 Trp Glu Ala Leu Glu Arg Ala Gly Ile Asp Pro His Thr Leu Arg Gly 2660 2665 2670 Ser Gln Thr Gly Val Tyr Ala Gly Met Phe His Gln Glu Tyr Ala Thr 2675 2680 2685 Arg Leu His Glu Ala Pro Val Glu Phe Glu Gly His Leu Leu Thr Gly 2690 2695 2700 Thr Ser Gly Ser Val Ala Ser Gly Arg Ile Ser Tyr Val Leu Gly Leu 2705 2710 2715 2720 Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val 2725 2730 2735 Ala Leu His Leu Ala Val Arg Ala Leu Arg Ser Gly Glu Cys Asp Leu 2740 2745 2750 Ala Leu Ala Gly Gly Val Thr Val Met Ala Glu Pro Gly Val Phe Val 2755 2760 2765 Glu Phe Ser Arg Gln Arg Gly Leu Ala Ala Asp Gly Arg Cys Lys Ala 2770 2775 2780 Phe Ala Ala Ala Ala Asp Gly Thr Gly Trp Ala Glu Gly Val Gly Val 2785 2790 2795 2800 Leu Ala Val Glu Arg Leu Ser Asp Ala Val Arg His Gly Arg Arg Val 2805 2810 2815 Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn 2820 2825 2830 Gly Leu Thr Ala Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Arg Gln 2835 2840 2845 Ala Leu Ala Asp Ala Arg Leu Gly Val Ala Asp Val Asp Val Val Glu 2850 2855 2860 Gly His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile Glu Ala Gln Ala 2865 2870 2875 2880 Leu Leu Ala Thr Tyr Gly Gln Arg Asp Ala Gly Arg Pro Leu Arg Leu 2885 2890 2895 Gly Ser Leu Lys Ser Asn Val Gly His Thr Gln Ala Ala Ala Gly Val 2900 2905 2910 Ala Gly Val Ile Lys Met Val Met Ala Met Arg His Gly Val Leu Pro 2915 2920 2925 Lys Thr Leu His Val Asp Glu Val Ser Pro His Val Asp Trp Ser Ala 2930 2935 2940 Gly Ala Val Ser Leu Leu Thr Glu Gln Glu Pro Trp Pro Arg Gly Glu 2945 2950 2955 2960 Arg Val Arg Arg Ala Gly Val Ser Ala Phe Gly Val Ser Gly Thr Asn 2965 2970 2975 Ala His Val Val Val Glu Glu Ala Pro Ala Ser Glu Ala Pro Val Ala 2980 2985 2990 Val Glu Pro Val Glu Pro Gly Ala Val Gly Leu Leu Pro Val Val Pro 2995 3000 3005 Val Val Val Ser Gly Arg Ser Ala Gly Ala Val Ala Glu Leu Ala Ser 3010 3015 3020 Arg Leu Asn Glu Ser Val Arg Ser Asp Arg Leu Val Asp Val Gly Leu 3025 3030 3035 3040 Ser Ser Val Val Ser Arg Ser Val Phe Glu His Arg Ser Val Val Leu 3045 3050 3055 Ala Gly Asp Ser Ala Glu Leu Ser Ala Gly Leu Asp Ala Leu Ala Ala 3060 3065 3070 Asp Gly Val Ser Pro Val Leu Val Ser Gly Val Ala Ser Val Gly Gly 3075 3080 3085 Gly Arg Ser Val Phe Val Phe Pro Gly Ala Gly Val Lys Trp Ala Gly 3090 3095 3100 Met Ala Leu Gly Leu Trp Ala Glu Ser Ala Val Phe Ala Glu Ser Met 3105 3110 3115 3120 Ala Arg Cys Glu Ala Ala Phe Ala Gly Leu Val Glu Trp Arg Leu Ala 3125 3130 3135 Asp Val Leu Gly Asp Gly Ala Ala Leu Glu Arg Glu Asp Val Val Gln 3140 3145 3150 Pro Ala Ser Phe Ala Val Met Val Ser Leu Ala Ala Leu Trp Arg Ser 3155 3160 3165 Leu Gly Val Val Pro Asp Ala Val Val Gly His Ser Gln Gly Glu Ile 3170 3175 3180 Ala Ala Ala Val Val Ala Gly Gly Leu Ser Leu Glu Asp Gly Ala Arg 3185 3190 3195 3200 Val Val Val Leu Arg Ala Arg Val Ala Glu Glu Val Leu Ser Gly Gly 3205 3210 3215 Gly Ile Ala Ser Val Arg Leu Ser Arg Ala Glu Val Glu Glu Arg Leu 3220 3225 3230 Ala Gly Gly Gly Gly Gly Leu Ser Val Ala Val Val Asn Ala Pro Ser 3235 3240 3245 Ser Thr Val Val Ala Gly Glu Leu Gly Glu Leu Asp Arg Phe Val Ala 3250 3255 3260 Ala Cys Glu Ala Glu Gly Val Arg Ala Arg Arg Leu Glu Phe Gly Tyr 3265 3270 3275 3280 Ala Ser His Ser Arg Phe Val Glu Pro Val Arg Glu Arg Leu Leu Glu 3285 3290 3295 Gly Leu Ala Asp Val Arg Pro Val Arg Gly Arg Ile Pro Phe Tyr Ser 3300 3305 3310 Thr Val Glu Ala Gly Glu Phe Asp Thr Ala Gly Leu Asp Ala Glu Tyr 3315 3320 3325 Trp Phe Gly Asn Leu Arg Arg Pro Val Arg Phe Gln Glu Thr Val Glu 3330 3335 3340 Arg Leu Leu Ala Asp Gly Phe Arg Val Phe Val Glu Cys Gly Ala His 3345 3350 3355 3360 Pro Val Leu Thr Gly Ala Val Gln Glu Thr Ala Glu Thr Ala Gly Arg 3365 3370 3375 Glu Val Cys Ala Val Gly Ser Leu Arg Arg Asp Glu Gly Gly Leu Arg 3380 3385 3390 Arg Phe Leu Thr Ser Ala Ala Glu Ala Phe Val Gln Gly Val Glu Val 3395 3400 3405 Ser Trp Pro Val Leu Phe Asp Gly Thr Gly Ala Arg Thr Val Asp Leu 3410 3415 3420 Pro Thr Tyr Pro Phe Gln Arg Arg His Tyr Trp Ala Gln Ser Ser Pro 3425 3430 3435 3440 Ala Gly Ala Gly Ser Ser Ala Ala Ala Arg Phe Gly Met Thr Trp Glu 3445 3450 3455 Glu His Pro Leu Leu Gly Gly Ala Leu Pro Leu Ala Asp Ser Gly Glu 3460 3465 3470 Leu Leu Leu Val Gly Arg Ile Ser Pro Ala Ser His Ser Trp Ile Ala 3475 3480 3485 Asp His Thr Val Ala Gly Thr Ala Leu Leu Pro Gly Thr Ala Phe Val 3490 3495 3500 Asp Met Ala Leu His Ala Ala Ala Val Ala Gly Cys Ala Gly Val Glu 3505 3510 3515 3520 Glu Leu Ser Ile Glu Ala Pro Leu Pro Val His Gly Gly Ile Arg Leu 3525 3530 3535 Gln Val Val Ile Asp Glu Pro Asp Ser Ser Ala Arg Arg Arg Val Ser 3540 3545 3550 Val Phe Ala Arg Pro Glu Glu Glu Asp Gly Asp Ala Gly Arg Trp Thr 3555 3560 3565 Arg His Ala Thr Gly Val Leu Thr Pro Asp Val Ala Pro Glu Pro Gly 3570 3575 3580 Arg Pro Gln Trp Cys Arg Gln Ala Trp Pro Pro Ser Gly Ser Val Arg 3585 3590 3595 3600 Val Glu Ala Ser Glu Leu Tyr Asp Arg Phe Ser Ala Leu Gly Tyr Asp 3605 3610 3615 Tyr Gly Glu Val Phe Ala Gly Val Glu Ala Val Trp Leu Arg Glu Gly 3620 3625 3630 Glu Ala Phe Ala Glu Val Arg Leu Pro Thr Gly Ala Ala Pro Asp Ala 3635 3640 3645 Glu Arg Phe Gly Val His Pro Gly Leu Leu Asp Ala Ala Leu His Pro 3650 3655 3660 Trp Leu Leu Gly Asp Phe Leu Ser Arg Pro Asp Gly Gly Ser Val Leu 3665 3670 3675 3680 Leu Pro Phe Ala Trp Arg Gly Ile Thr Leu His Thr Ala Gly Ala Asp 3685 3690 3695 Ala Leu Arg Val Arg Leu Gly Pro Ala Gly Glu Gly Ala Leu Ser Leu 3700 3705 3710 Glu Ala Val Asp Leu Ser Gly Ala Pro Val Leu Ser Met Asp Ala Leu 3715 3720 3725 Val Leu Arg Pro Leu Ala Gln Asp Arg Leu Ala Glu Leu Val Gly Gly 3730 3735 3740 Thr Thr Ser Thr Pro Leu Tyr Arg Val Asp Trp Gln Arg Ser Pro Ile 3745 3750 3755 3760 Ala Arg Thr Ala Pro Ser Ala Thr Gly Leu Phe Gly Ser Leu Pro Ser 3765 3770 3775 Gly Ala Val Arg Arg Trp Ala Val Val Gly Gln Gly Gly Val Ala Ala 3780 3785 3790 Arg Tyr Ala Thr Ala Glu Pro Gly Thr Gly Cys Val Gly Val Phe Pro 3795 3800 3805 Asp Leu Asp Ala Leu Arg Thr Thr Leu Asp Ser Gly Ala Asp Gly Pro 3810 3815 3820 Asp Ile Val Leu Ala Asp Phe Gly Ala Arg Pro Gly Asp Ala Ala Pro 3825 3830 3835 3840 His Gly Thr Asp Pro Ala Asp Gly Ala Arg Asp Thr Val Arg Arg Gly 3845 3850 3855 Leu Ala Leu Ile Gln Gly Trp Leu Ser Asp Glu Arg Phe Ala Ala Ala 3860 3865 3870 Arg Leu Ala Val Leu Thr Glu His Ala Val Ala Thr Glu Ala Asp Thr 3875 3880 3885 Arg Arg Thr Asp Leu Ala Gly Ser Ala Leu Trp Gly Leu Met Arg Ser 3890 3895 3900 Ala Gln Thr Glu His Pro Asp Arg Phe Val Leu Val Asp His Asp Gly 3905 3910 3915 3920 Gln Asp Ala Ser Tyr Arg Thr Leu Pro Thr Ala Leu Asp Ser Glu Ile 3925 3930 3935 Pro Gln Leu Ala Leu Arg Ala Gly Glu Thr Leu Ala Pro Glu Leu Ala 3940 3945 3950 Val Leu Pro Ser Pro Ala Asp Gly Gly Pro Ala Thr Ser Ala Ala Phe 3955 3960 3965 Asp Pro Glu Gly Thr Val Leu Val Thr Gly Ala Thr Gly Thr Leu Gly 3970 3975 3980 Ser Leu Leu Ala Arg His Leu Val Thr Ala His Gly Val Arg His Leu 3985 3990 3995 4000 Leu Leu Leu Ser Arg Ser Gly Arg Glu Ala Ala Gly Ala Ala Glu Leu 4005 4010 4015 Glu Arg Glu Leu Arg Gln Arg Gly Ala Glu Phe Gln Leu Leu Ser Cys 4020 4025 4030 Asp Ala Thr Asp Arg Ala Ala Leu Lys Glu Ala Leu Ala Thr Val Pro 4035 4040 4045 Ala Ala His Pro Leu Thr Ala Val Ile His Thr Ala Gly Val Leu Asp 4050 4055 4060 Asp Gly Val Val Glu Ala Leu Thr Pro Glu Arg Leu Asp Arg Val Leu 4065 4070 4075 4080 Arg Pro Lys Ala Asp Ala Ala Leu Asn Leu His Asp Leu Thr Glu Gly 4085 4090 4095 Met Pro Leu Lys Ala Phe Val Leu Tyr Ser Gly Ala Val Gly Leu Leu 4100 4105 4110 Gly Gly Ala Gly Gln Ala Asn Tyr Ala Ala Ala Asn Ala Phe Leu Asp 4115 4120 4125 Gly Leu Ala Gln His Arg His Ala Gln Gly Leu Pro Ala Val Ser Leu 4130 4135 4140 Ala Trp Gly Leu Trp Ser Ala Thr Ser Thr Phe Thr Asp His Leu Gly 4145 4150 4155 4160 Glu Val Asp Leu Arg Arg Met Glu Arg Ser Gly Ile Thr Pro Leu Thr 4165 4170 4175 Asp Glu Gln Gly Leu Asp Leu Phe Asp Arg Ala Leu Gly Ala Ala Val 4180 4185 4190 Asp Ala Pro Gln Leu Cys Val Met Gly Leu Asp Thr Ala Ala Leu Arg 4195 4200 4205 Arg Gln Ala Ala Glu His Gly Pro Thr Ser Met Pro Pro Leu Leu Arg 4210 4215 4220 Thr Leu Ala Ala Pro Pro Val Arg Arg Gly Ala Gly Arg Ser Gly Arg 4225 4230 4235 4240 Gly Gly Arg Ala Ala Ser Ala Thr Asp Ala Pro Ser Arg Ala Gln Ala 4245 4250 4255 Leu Arg Glu Arg Leu Thr Gly Leu Asp Ala Ala Ala Arg Arg Asp Glu 4260 4265 4270 Leu Leu Val Leu Ser Gln Ala Gln Leu Ala Asp Val Leu Gly Phe Ala 4275 4280 4285 Asp Lys Thr Ala Val Asp Pro Val Arg Ser Phe Arg Glu Ile Gly Leu 4290 4295 4300 Asp Ser Leu Thr Ala Val Glu Leu Arg Asn Arg Leu Gly Val Val Thr 4305 4310 4315 4320 Gly Leu Arg Leu Pro Pro Ala Leu Val Phe Asp His Pro Asn Leu Asp 4325 4330 4335 Ala Leu Ala Ala His Leu Ala Glu Leu Leu Ala Ala Glu Gly Arg Asp 4340 4345 4350 Asp Ala Gly Ala Ala Ala Leu Ser Gly Ile Asp Ala Leu Asp Arg Ala 4355 4360 4365 Val Arg Glu Met Ala Ala Asp Asp Thr Arg Arg Asp Ala Val Arg Arg 4370 4375 4380 Arg Leu Ala Glu Leu Leu Ala Val Val Gly Asp Ala Pro Arg Asp Gly 4385 4390 4395 4400 Gly Arg Ala Pro Arg Ala Ala Ala Asp Ala Gly Gly Arg Asp Ala Gln 4405 4410 4415 Ala Asp Pro Asp Leu Leu Gly Arg Leu Asp Ser Ala Ser Asp Asp Asp 4420 4425 4430 Leu Phe Ala Phe Ile Glu Asp Gln Leu 4435 4440 24 1974 PRT Streptomyces bikiniensis 24 Met Thr Ala Asn Asp Asp Lys Ile Arg Asp Tyr Leu Lys Arg Val Val 1 5 10 15 Ala Glu Leu His Ser Thr Arg Gln Arg Leu Asn Ala Leu Glu His Asp 20 25 30 Ala Arg Glu Pro Ile Ala Ile Val Gly Met Ser Cys Arg Leu Pro Gly 35 40 45 Gly Val Thr Thr Pro Glu Ser Leu Trp Arg Leu Val Asp Ser Gly Thr 50 55 60 Asp Ala Ala Ser Pro Phe Pro Asp Asp Arg Gly Trp Asp Leu Asp Ala 65 70 75 80 Leu His His Pro Glu Ser Gly Ala Val His Ser Arg Glu Gly Gly Phe 85 90 95 Leu His Asp Ser Ala Asp Phe Asp Ala Glu Phe Phe Gly Ile Ser Pro 100 105 110 Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu Leu Leu Glu Thr 115 120 125 Ala Trp Glu Val Phe Glu Arg Ala Gly Ile Asp Pro Val Ser Ala Arg 130 135 140 Gly Ser Arg Thr Gly Val Tyr Ala Gly Val Met Tyr His Asp Tyr Gly 145 150 155 160 Ala Arg Leu Asn Glu Ile Pro Pro Gly Leu Glu Gly Tyr Leu Val Asn 165 170 175 Gly Ser Ala Gly Ser Ile Ala Ser Gly Arg Val Ala Tyr Thr Leu Gly 180 185 190 Leu Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu 195 200 205 Val Ala Val His Leu Ala Ala Gln Ala Leu Arg Arg Arg Glu Cys Asp 210 215 220 Met Ala Leu Ala Gly Gly Ala Thr Val Leu Ser Thr Pro Asp Leu Phe 225 230 235 240 Ile Asp Phe Ala Arg Leu Gly Gly Leu Ala Ser Asp Gly Arg Cys Lys 245 250 255 Ala Phe Ser Asp Ala Ala Asp Gly Thr Ser Phe Ala Glu Gly Ala Gly 260 265 270 Leu Leu Leu Leu Met Arg Leu Ser Asp Ala Val Ala Glu Gly His Thr 275 280 285 Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser 290 295 300 Asn Gly Leu Thr Ala Pro Asn Gly Leu Ala Gln Gln Arg Val Ile Arg 305 310 315 320 Glu Ala Leu Ala Asp Ala Asp Leu Asp Pro Asp Gln Ile Asp Ala Val 325 330 335 Glu Ala His Gly Thr Gly Thr Arg Leu Gly Asp Pro Ile Glu Ala Gln 340 345 350 Ala Leu Leu His Thr Tyr Gly Thr Ser Arg Ser Pro Glu Arg Pro Leu 355 360 365 Trp Leu Gly Ser Leu Lys Ser Asn Ile Gly His Thr Gln Ala Ala Ala 370 375 380 Gly Val Ala Gly Val Ile Lys Thr Val Leu Ala Met Arg His Gly Arg 385 390 395 400 Leu Pro Arg Thr Leu His Val Thr Arg Pro Ser Ser Arg Val Glu Trp 405 410 415 Ser Ala Gly Ala Val Glu Leu Leu Thr Arg Ala Gln Asp Trp Pro Gly 420 425 430 Gln Gly Asn Ala Pro Arg Arg Ala Gly Val Ser Ser Phe Gly Ala Ser 435 440 445 Gly Thr Asn Ala His Leu Ile Leu Glu Gly Val Pro Asp Gly Asp Ile 450 455 460 Thr Val Ala Glu Thr Arg Pro Ala Thr Gly Gly Gly Ala Trp Pro Leu 465 470 475 480 Ala Gly Arg Thr Glu Ala Ala Leu Arg Ala Gln Ala Arg Arg Leu His 485 490 495 Asp His Leu Ala Ala Arg Pro His Val Ser Pro Ala Ala Val Gly Arg 500 505 510 Thr Leu Val Arg Ser Arg Thr Ala Phe Glu His Arg Ala Val Val Leu 515 520 525 Gly Gln Asp Thr Ala Asp Leu Leu Ser Gly Leu Ala Glu Leu Ala Ser 530 535 540 Gly Gly Ala His Gly Pro Gly Val Ile Thr Gly Arg Ala Ala Arg Gly 545 550 555 560 Arg Arg Thr Ala Leu Leu Phe Thr Gly Gln Gly Ser Gln Arg Pro Gly 565 570 575 Ala Gly Arg His Leu Tyr Glu Arg Tyr Glu Val Phe Ala Arg Ala Leu 580 585 590 Asp Glu Thr Ala Ala Ala Leu Asp Arg His Leu Asp Arg Pro Leu Arg 595 600 605 Asp Val Met Phe Ala Glu Pro Gly Gly Ala Thr Ala Gly Leu Leu Asp 610 615 620 Arg Thr Glu Tyr Thr Gln Pro Ala Leu Phe Ala Leu Glu Val Ala Leu 625 630 635 640 Phe Arg Leu Val Thr Ala Gly Gly Leu Arg Pro Asp Ala Leu Leu Gly 645 650 655 His Ser Val Gly Glu Leu Ala Ala Ala His Val Ala Gly Val Phe Thr 660 665 670 Leu Pro Asp Ala Ala Arg Leu Val Thr Ala Arg Gly Arg Leu Met Gly 675 680 685 Glu Leu Pro Ala Gly Gly Ala Met Met Ala Ile Gln Ala Ser Gly Pro 690 695 700 Glu Ile Glu Glu Thr Ile Thr Ala Leu Ala Ala His Arg Ser Ala Arg 705 710 715 720 Val Ala Val Ala Ala Leu Asn Gly Pro Asp Ala Thr Val Ile Ser Gly 725 730 735 Asp Glu Asp Val Val Ala Glu Leu Ala Thr Leu Trp Arg Glu Arg Gly 740 745 750 Arg Arg Thr Arg Ala Leu Pro Val Ser His Ala Phe His Ser Pro His 755 760 765 Met Asp Ala Ala Leu Glu Pro Phe Ala Arg Ile Ala Arg Asp Val Ser 770 775 780 Tyr Ala Glu Pro Arg Ile Pro Val Val Ser Asn Leu Thr Gly Gly Ile 785 790 795 800 Ala Ser Ala Thr Thr Leu Cys Ala Pro Glu Tyr Trp Val Arg His Ala 805 810 815 Arg Glu Ala Val Arg Phe Ser Asp Gly Phe Arg Ala Leu Arg Asp Gln 820 825 830 Gly Ile Asp Thr Phe Ile Glu Leu Gly Pro Asp Gly Val Leu Ser Ala 835 840 845 Leu Gly Arg Asp Cys Leu Arg Glu Glu Glu Gly Asp Ala Pro Arg Gln 850 855 860 Asp Gly Ser Ala Asp Pro Asp Thr Thr Gly Ser Arg Ala Asp Gly Gly 865 870 875 880 Arg Arg Pro Val Leu Thr Val Pro Leu Leu Arg Arg Asp Arg Asp Glu 885 890 895 Thr Thr Thr Cys Leu Gly Ala Leu Ala Thr Val His Thr His Gly Val 900 905 910 Pro Val Asp Leu Ala Ala Val His Gly Ala Pro Glu Gly Pro Ala Val 915 920 925 Glu Leu Pro Thr Tyr Ala Phe Gln Arg Thr Arg Tyr Trp Leu Asp Ala 930 935 940 Pro Ala Pro Ala Ala Gly Pro Thr Ala Thr Gly Leu Glu Ala Thr Asp 945 950 955 960 Gln Pro Leu Leu Pro Ala Val Ile Asp Leu Pro Asp Gly Glu Gly Thr 965 970 975 Val Arg Thr Gly Leu Leu Ser Leu Arg Thr His Pro Trp Ile Ala Asp 980 985 990 His Arg Val Arg Asp His Ala Val Val Pro Gly Ala Ala Leu Leu Asp 995 1000 1005 Val Ala Ala Trp Ala Gly Thr Glu Ala Gly Cys Pro Arg Val Ala Glu 1010 1015 1020 Leu Thr Phe Ala Thr Pro Leu Val Leu Pro Glu Asn Gly Glu Gly Val 1025 1030 1035 1040 Arg Leu Arg Val Thr Val Ser Gly Pro Asp Ala Glu Gly Ile Arg Ser 1045 1050 1055 Leu Arg Ile Asp Ser Arg Pro Ala Asp Thr Val Arg Thr Ala Asp Ala 1060 1065 1070 Pro Ser Asp Trp Thr Arg His Ala Ser Gly Thr Leu Val Pro Ala Pro 1075 1080 1085 Glu Glu Ala Gly Asp Gly Thr Gly Val Pro Thr Glu Leu Leu Gly Ala 1090 1095 1100 Trp Pro Pro Ala Asp Ala Thr Pro Val Ala Leu Asp Ala Asp Ala Val 1105 1110 1115 1120 Ala Ala Glu Tyr Gln Arg Leu Ala Ala Gly Gly Val Thr Tyr Gly Pro 1125 1130 1135 Ala Phe Arg Ala Leu Arg Ala Val Trp Arg Arg Gly Ala Glu Val Phe 1140 1145 1150 Ala Glu Val Arg Leu Pro Gly Gln Ala Ala Ala Asp Ala Ser Arg Tyr 1155 1160 1165 Gly Met His Pro Ala Leu Leu Asp Ala Leu Thr His Ala Thr Gly Phe 1170 1175 1180 Gly Glu Arg Ser Thr Glu Ala Arg Gly Leu Val Pro Phe Ala Trp Ser 1185 1190 1195 1200 Asp Val Arg Ile His Val Arg Gly Ala Asp Ser Leu Arg Val Arg Ile 1205 1210 1215 Ala Pro Ala Gly Pro Asp Ala Val Thr Val Ala Ala Val Asp Pro Thr 1220 1225 1230 Gly Arg Pro Val Leu Ala Ala Arg Ser Leu Thr Leu Arg Pro Leu Ala 1235 1240 1245 Glu Ser Arg Phe Gln Asp Pro Glu Ala Asp Ser Thr Pro Leu Tyr Arg 1250 1255 1260 Leu Glu Trp Thr Pro Ala Pro Gly Ser Val Thr Gly His Ala Gly Pro 1265 1270 1275 1280 Arg Gln Ala Ala Ala Glu Trp Gly Val Leu Gly Asp Pro Val Gln Ala 1285 1290 1295 Leu Leu Asp Ala Val Arg Asp Gly Ala Glu Ala Pro Val Arg Thr His 1300 1305 1310 Asp Asp Leu Leu Ala Leu Ala Ala Ser Asp Thr Ala Pro Pro Asp His 1315 1320 1325 Val Leu Ala Leu Leu Gly His Asp Gly Asp Ala Leu Ala Thr Gly Ala 1330 1335 1340 His Asp Leu Ala Ala Arg Ala Leu Ala Leu Val Gln Gly Trp Leu Thr 1345 1350 1355 1360 His Ala Arg Phe Ala Asp Ala Arg Leu Val Val Leu Thr Gln Gly Ala 1365 1370 1375 Val Thr Ala Gly Thr Ser Pro Val His Pro Ala Ala Ala Ala Ala Trp 1380 1385 1390 Gly Leu Leu Arg Ser Ala Gln Ser Glu His Pro Gly Arg Phe Val Leu 1395 1400 1405 Val Asp Ala Asp Pro Ala Asp Pro Ala Ala Ser Tyr Arg Ser Leu Pro 1410 1415 1420 Arg Ala Val Ala Ser Gly Ala Ser Gln Leu Ala Leu Arg Gly Ala Glu 1425 1430 1435 1440 Ile Leu Val Pro Arg Leu Ala Arg Gly Thr Asp Arg Gln Ala Thr Val 1445 1450 1455 Pro Gly His Pro Gly Asp Val Thr Ala Pro Glu Thr Thr Ala Ala Pro 1460 1465 1470 Glu Pro Ala Pro Ser Gly Thr Pro Ser Gly Pro Trp Pro Ala Asp Gly 1475 1480 1485 Thr Val Leu Val Thr Gly Gly Thr Gly Thr Leu Gly Lys Ala Val Ala 1490 1495 1500 Arg His Leu Val Thr Lys His Gly Val Arg His Leu Ile Leu Ala Gly 1505 1510 1515 1520 Arg Arg Gly Ala Asp Thr Pro Gly Ala Ala Asp Leu Ala Thr Glu Leu 1525 1530 1535 Thr Gly Leu Gly Ala Thr Val Asn Ile Val Arg Cys Asp Ala Ala Asp 1540 1545 1550 Arg Ser Ala Leu Glu Gly Val Leu Ala Ala Val Pro Ala Ala His Pro 1555 1560 1565 Leu Thr Ala Val Val His Thr Ala Gly Val Leu Asp Asp Gly Ile Val 1570 1575 1580 Thr Ala Gln Thr Pro Arg Arg Leu Ser Ala Val Leu Arg Ala Lys Ala 1585 1590 1595 1600 Asp Ala Val Ser His Leu His Glu Leu Thr Arg Asp Leu Asp Leu Ser 1605 1610 1615 Ala Phe Val Leu Phe Ser Ser Ala Ala Gly Thr Leu Gly Ser Pro Gly 1620 1625 1630 Gln Ser Gly Tyr Ala Ala Ala Asn Ser Phe Leu Asp Ala Phe Ala Ala 1635 1640 1645 Trp Arg Arg Ala Gln Gly Leu Pro Ala Val Ser Leu Ala Trp Gly Leu 1650 1655 1660 Trp Gly Asp Gly Gly Asp Gly Arg Asp Gly Gly Gly Ser Ala Ala Asp 1665 1670 1675 1680 Gly Met Gly Ala Ser Leu Ala Ala Ala Asp Leu Ala Arg Leu Arg Arg 1685 1690 1695 Ser Gly Ile Leu Pro Leu Asp Pro Ala Glu Ala Leu Arg Leu Phe Asp 1700 1705 1710 Glu Ala Cys Asp Pro Ala Arg Thr Glu Ala Val Leu Leu Pro Ile Arg 1715 1720 1725 Leu Asp Leu Thr Gly Leu Arg Ala Arg Ser Ala Arg Gly Ala Val His 1730 1735 1740 Ala Ser Val Val Pro Glu Val Leu His Thr Leu Val Pro Pro Pro Ala 1745 1750 1755 1760 Gly Ala Gly Ser Pro Ala Gly Ala Asp Ala Ser Asp Pro Ala Ala Gly 1765 1770 1775 Gln Ala Pro Pro Ala Pro Ala Ser Asp Thr Leu Ala Glu Arg Leu Ala 1780 1785 1790 Gly Lys Pro Arg Gly Glu Arg Leu Thr Ala Leu Thr Glu Leu Val Arg 1795 1800 1805 Thr Glu Ile Ala Ser Val Leu Gly His Pro Asp Ser Gly Arg Val Gln 1810 1815 1820 Leu Gln Ser Ser Phe Lys Glu Ser Gly Phe Asp Ser Leu Thr Ala Val 1825 1830 1835 1840 Glu Leu Arg Asn Arg Leu Thr Ala Ala Thr Gly Thr Lys Leu Pro Ala 1845 1850 1855 Thr Leu Val Phe Asp His Pro Thr Pro Ala Ala Leu Val Asp His Leu 1860 1865 1870 Glu Gln Glu Leu Pro Lys Ala Ala Gln Glu Ile Pro Ala Asp Leu Pro 1875 1880 1885 Ala Val Leu Asp Ala Leu Asp Arg Ile Arg Asp Gly Leu Ala Thr Ala 1890 1895 1900 Ala Thr Asp Asp Ser Ser Arg Asp His Ile Ala Glu Arg Leu Gln Ala 1905 1910 1915 1920 Leu Leu Gly Thr Leu Thr Ser Ala Ala Gly Val Ser Arg Pro Thr Gly 1925 1930 1935 Ser Pro Gly Glu His Asp Arg Gln Gly Pro Asp Glu Leu Ser Leu Gly 1940 1945 1950 Gln Arg Leu Ala Ala Ser Ser Asp Asp Glu Leu Phe Asp Leu Phe Asp 1955 1960 1965 Ser Asp Phe Arg Ser Thr 1970 25 3788 PRT Streptomyces bikiniensis 25 Met Ser Ser Thr Ser Pro Ala Thr Asn Glu Glu Lys Leu Arg Asp Tyr 1 5 10 15 Leu Arg Arg Ala Met Thr Asp Leu His Glu Ala Arg Glu Gln Ile Arg 20 25 30 Arg Thr Glu Ser Ala Arg His Glu Pro Ile Ala Ile Val Gly Met Gly 35 40 45 Cys Arg Leu Pro Gly Gly Val Ser Ser Pro Glu Gly Leu Trp Asp Leu 50 55 60 Val Ala Ser Gly Val Asp Ala Val Ser Pro Phe Pro Thr Asp Arg Gly 65 70 75 80 Trp Asp Val Gly Gly Leu Phe Asp Pro Glu Pro Gly Val Pro Gly Arg 85 90 95 Ser Tyr Val Arg Glu Gly Gly Phe Leu His Glu Ala Gly Glu Phe Asp 100 105 110 Ala Gly Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro 115 120 125 Gln Gln Arg Leu Leu Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala 130 135 140 Gly Ile Asp Pro His Thr Leu Arg Gly Ser Arg Thr Gly Val Tyr Ala 145 150 155 160 Gly Val Met Tyr His Asp Tyr Gly Ser Thr Ala Thr Val Ser Val Ala 165 170 175 Ser Asp Asp Glu Thr Ala Gly Phe Leu Gly Thr Gly Thr Ser Gly Ser 180 185 190 Val Ala Ser Gly Arg Ile Ser Tyr Val Leu Gly Leu Glu Gly Pro Ala 195 200 205 Val Thr Val Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu 210 215 220 Ala Val Arg Ala Leu Arg Ser Gly Glu Cys Asp Leu Ala Leu Ala Gly 225 230 235 240 Gly Val Thr Val Met Ala Glu Pro Gly Val Phe Val Glu Phe Ser Arg 245 250 255 Gln Arg Gly Leu Ala Ala Asp Gly Arg Cys Lys Ala Phe Ala Ala Ala 260 265 270 Ala Asp Gly Thr Gly Trp Ala Glu Gly Val Gly Val Leu Ala Val Glu 275 280 285 Arg Leu Ser Asp Ala Val Arg His Gly Arg Arg Val Leu Ala Val Val 290 295 300 Arg Gly Ser Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala 305 310 315 320 Pro Asn Gly Pro Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Asp 325 330 335 Ala Arg Leu Gly Val Ala Asp Val Asp Val Val Glu Gly His Gly Thr 340 345 350 Gly Thr Arg Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr 355 360 365 Tyr Gly Gln Arg Asp Ala Gly Arg Ala Leu Arg Leu Gly Ser Leu Lys 370 375 380 Ser Asn Val Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile 385 390 395 400 Lys Met Val Met Ala Met Arg His Gly Val Leu Pro Lys Thr Leu His 405 410 415 Val Asp Glu Pro Thr Ala Glu Val Asp Trp Ser Ala Gly Ala Val Ser 420 425 430 Leu Leu Arg Glu Gln Glu Ala Trp Pro Glu Val Gly Arg Leu Arg Arg 435 440 445 Ala Ala Val Ser Ser Phe Gly Val Ser Gly Thr Asn Ala His Val Val 450 455 460 Val Glu Glu Ala Pro Ala Ser Glu Ala Pro Val Ala Gly Glu Pro Val 465 470 475 480 Glu Pro Val Glu Pro Gly Ala Val Gly Leu Leu Pro Val Val Pro Val 485 490 495 Val Val Ser Gly Arg Ser Ala Gly Ala Val Ala Glu Leu Ala Ser Arg 500 505 510 Leu Asn Glu Ser Val Arg Ser Asp Arg Leu Val Asp Val Gly Leu Ser 515 520 525 Ser Val Val Ser Arg Ser Val Phe Glu His Arg Ser Val Val Leu Ala 530 535 540 Glu Asp Ser Ala Glu Leu His Thr Gly Leu Val Ala Val Gly Thr Gly 545 550 555 560 Val Pro Ser Pro Gly Val Val Ser Gly Val Ala Ser Val Glu Gly Gly 565 570 575 Arg Ser Val Phe Val Phe Pro Gly Gln Gly Thr Gln Trp Ala Gly Met 580 585 590 Ala Leu Gly Leu Trp Ala Glu Ser Ala Val Phe Ala Glu Ser Met Ala 595 600 605 Arg Cys Glu Ala Ala Phe Ala Gly Leu Val Asp Trp Arg Leu Ala Asp 610 615 620 Val Leu Gly Asp Arg Ser Ala Leu Glu Arg Val Asp Val Val Gln Pro 625 630 635 640 Ala Ser Phe Ala Val Met Val Ser Leu Ala Glu Leu Trp Arg Ser Leu 645 650 655 Gly Val Val Pro Asp Ala Val Val Gly His Ser Gln Gly Glu Ile Ala 660 665 670 Ala Ala Val Val Ala Gly Gly Leu Ser Leu Glu Asp Gly Ala Arg Val 675 680 685 Val Val Leu Arg Ala Arg Leu Ile Gly Arg Glu Leu Ala Gly His Gly 690 695 700 Gly Met Ala Ser Val Ala Leu Pro Val Ala Val Val Glu Glu Arg Leu 705 710 715 720 Ala Ala Trp Ala Gly Arg Leu Gly Val Ala Val Val Asn Ala Pro Ser 725 730 735 Ala Thr Val Val Ala Gly Asp Val Asp Ala Val Ala Glu Phe Val Thr 740 745 750 Ala Cys Glu Val Glu Gly Val Arg Ala Arg Val Leu Pro Val Asp Tyr 755 760 765 Ala Ser His Ser Ala His Val Glu Glu Leu Arg Ala Glu Leu Glu Gln 770 775 780 Ile Leu Ala Gly Ile Asp Pro Val Ala Gly Glu Thr Pro Leu Tyr Ser 785 790 795 800 Thr Val Glu Ala Gly Val Val Asp Thr Ala Ser Met Asp Ala Gly Tyr 805 810 815 Trp Phe Arg Asn Leu Arg Arg Pro Val Arg Phe Gln Glu Thr Val Glu 820 825 830 Arg Leu Leu Ala Asp Gly Phe Arg Val Phe Val Glu Cys Gly Ala His 835 840 845 Pro Val Leu Thr Gly Ala Val Gln Glu Thr Ala Glu Ser Thr Gly Arg 850 855 860 Gln Val Cys Ala Val Gly Ser Leu Arg Arg Asp Glu Gly Gly Leu Arg 865 870 875 880 Arg Phe Leu Thr Ser Ala Ala Glu Ala Phe Val Gln Gly Val Glu Val 885 890 895 Ser Trp Pro Val Leu Phe Asp Gly Thr Gly Ala Arg Thr Val Asp Leu 900 905 910 Pro Thr Tyr Pro Phe Gln Arg Arg Arg Tyr Trp Leu Glu Ser Arg Pro 915 920 925 Pro Ala Ala Val Val Pro Ser Gly Val Gln Asp Gly Leu Ser Tyr Glu 930 935 940 Val Val Trp Lys Ser Leu Pro Val Arg Glu Ser Ser Arg Leu Asp Gly 945 950 955 960 Arg Trp Leu Leu Val Val Pro Glu Thr Leu Asp Ala Asp Gly Thr Arg 965 970 975 Ile Ala His Asp Leu Gln His Ala Leu Thr Thr His Gly Ala Thr Val 980 985 990 His Thr Leu Ala Leu Asp Pro Ser Ala Ala His Phe Asp Gly Leu Phe 995 1000 1005 Asp Gly Ile Leu Gln Glu Glu Thr Asp Val Thr Gly Ile Phe Ser Leu 1010 1015 1020 Leu Gly Leu Ala Ser Gly Pro His Pro Asp His Gly Glu Val Glu Leu 1025 1030 1035 1040 Ala Gly Ala Ala Ser Leu Thr Leu Met Arg Gln Ala Gln Arg Asp Gly 1045 1050 1055 Phe Arg Ala Pro Val Trp Ala Val Thr Arg Gly Ala Val Ser Val Val 1060 1065 1070 Pro Gly Glu Val Pro Glu Thr Ala Gly Ala Gln Leu Trp Ala Leu Gly 1075 1080 1085 Arg Val Ala Gly Leu Glu Leu Pro Asp Arg Trp Gly Gly Leu Ile Asp 1090 1095 1100 Leu Pro Ala Asp Ala Asp Ala Arg Thr Ala Gly Leu Ala Val Arg Ala 1105 1110 1115 1120 Leu Ala Ala Gly Ile Ala Asp Gly Glu Asp Gln Leu Ala Val Arg Pro 1125 1130 1135 Ser Gly Ala Tyr Gly Arg Arg Leu Val Arg Ala Thr Ala Arg Arg Gly 1140 1145 1150 Arg Lys Asp Trp Arg Pro Gln Gly Thr Val Leu Leu Ala Gly His Leu 1155 1160 1165 Asp Ala Val Gly Glu Pro Leu Ala Arg Trp Leu Leu Thr Gly Gly Ala 1170 1175 1180 Asp His Val Val Leu Ala Asp Pro Ala Leu Thr Glu Leu Pro Ala Thr 1185 1190 1195 1200 Leu Ala Asp Leu Ala Gln Thr Val Thr Thr Ala Ala Ala Pro Asp Leu 1205 1210 1215 Ala Asp Arg Ala Val Leu Ala Ala Leu Val Thr Glu Tyr Val Pro Ala 1220 1225 1230 Thr Val Val Val Val Pro Pro Ala Ala Glu Leu Ala Pro Leu Ala Ser 1235 1240 1245 Ile Ser Pro Ala Asp Leu Ala Ala Ala Val Thr Ala Lys Ser Ala Thr 1250 1255 1260 Ala Ala His Phe Asp Ala Leu Leu Asp Gly Pro His Ala Pro Glu Leu 1265 1270 1275 1280 Val Leu Ile Ser Ser Val Ala Gly Ile Trp Gly Gly Val Arg Gln Gly 1285 1290 1295 Ala Tyr Ala Val Gly Ala Ala His Leu Asp Ala Leu Ala Ala Arg Arg 1300 1305 1310 Arg Ala Arg Gly Leu Ser Ala Ala Ser Val Ala Trp Thr Pro Trp Ala 1315 1320 1325 Gly Ser Val Thr Ala Asp Gly Ser Ala Ala Glu Ser Leu Arg Gln Tyr 1330 1335 1340 Gly Ile Ala Pro Leu Glu Pro Gln Ala Ala Leu Ala Glu Leu Asp Arg 1345 1350 1355 1360 Ala Leu Asn Gln Gln Leu His Gly Gly Gly Gly Asp Ala Ala Val Ala 1365 1370 1375 Asp Ile Asp Trp Glu Arg Phe Leu Ala Ser Phe Thr Ser Val Arg Pro 1380 1385 1390 Ser Val Leu Phe Asp Glu Leu Pro Glu Val Arg Arg Leu Arg Glu Ala 1395 1400 1405 Glu Ala Ala Ala Met Ala Asp Gln Ala Ala Ala Arg Thr Gly Ala Pro 1410 1415 1420 Gly Gly Thr Glu Leu Ala Arg Ser Leu Arg Ala Lys Ser Leu Asn Ala 1425 1430 1435 1440 Gln Arg Thr Ala Leu Leu Glu Leu Val Thr Ala His Val Ala Ala Val 1445 1450 1455 Leu Gly Glu Ser Val Pro Glu Ala Ile Asp Arg Ser Arg Ala Phe Lys 1460 1465 1470 Asp Ile Gly Phe Thr Ser Met Thr Ala Met Glu Leu Arg Asn Arg Leu 1475 1480 1485 Lys Glu Ala Thr Gly Leu Ala Leu Pro Ala Ser Leu Val Phe Asp His 1490 1495 1500 Pro His Pro Gly Ala Leu Ala Asp His Leu Arg Glu Glu Leu Leu Gly 1505 1510 1515 1520 Glu Asp Gly Ala Ala Gly Ala Asp Ser Ala Ala Glu Glu Pro Ser Ala 1525 1530 1535 Thr Ser Pro Thr Val Gln Asp Glu Pro Ile Ala Ile Ile Gly Met Ala 1540 1545 1550 Cys Arg Leu Pro Gly Asp Val Gly Thr Pro Asp Glu Leu Trp Glu Leu 1555 1560 1565 Leu Glu Thr Gly Arg Asp Ala Met Ser Asp Leu Pro Val Asn Arg Gly 1570 1575 1580 Trp Asp Val Ala Gly Leu Tyr Asp Pro Asp Pro Asp Ala Ala Gly Arg 1585 1590 1595 1600 Ser Tyr Val Arg Glu Gly Gly Phe Leu His Asp Ala Gly Glu Phe Asp 1605 1610 1615 Ala Glu Phe Phe Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro 1620 1625 1630 Gln Gln Arg Ile Val Leu Glu Leu Ala Trp Glu Ser Phe Glu Arg Ala 1635 1640 1645 Gly Leu Asp Pro Ala Gly Arg Arg Gly Ser Arg Thr Gly Val Phe Met 1650 1655 1660 Gly Thr Asn Gly Gln His Tyr Met Pro Leu Leu Gln Asn Gly Asn Asp 1665 1670 1675 1680 Ser Phe Asp Gly Tyr Leu Gly Thr Gly Asn Ser Ala Ser Val Met Ser 1685 1690 1695 Gly Arg Ile Ser Tyr Thr Leu Gly Leu Glu Gly Pro Ala Leu Thr Val 1700 1705 1710 Asp Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Val Arg 1715 1720 1725 Ala Leu Arg Asn Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly Ala Thr 1730 1735 1740 Val Met Ser Thr Pro Glu Val Leu Val Glu Phe Ser Arg Gln Arg Ala 1745 1750 1755 1760 Val Ser Ala Asp Gly Arg Cys Lys Ala Phe Ser Ala Ser Ala Asp Gly 1765 1770 1775 Phe Gly Pro Ala Glu Gly Ala Gly Val Leu Leu Val Glu Arg Leu Ser 1780 1785 1790 Asp Ala Val Arg His Gly Arg Arg Val Leu Ala Val Val Arg Gly Ser 1795 1800 1805 Ala Val Asn Gln Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Asn Gly 1810 1815 1820 Pro Ser Gln Gln Arg Val Ile Arg Gln Ala Leu Ala Asp Ala Arg Leu 1825 1830 1835 1840 Gly Val Ala Asp Val Asp Val Val Glu Gly His Gly Thr Gly Thr Arg 1845 1850 1855 Leu Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln 1860 1865 1870 Arg Asp Ala Gly Arg Pro Leu Arg Leu Gly Ser Leu Lys Ser Asn Val 1875 1880 1885 Gly His Thr Gln Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val 1890 1895 1900 Met Ala Met Arg His Gly Val Leu Pro Lys Thr Leu His Val Asp Glu 1905 1910 1915 1920 Val Ser Pro His Val Asp Trp Ser Ala Gly Ala Val Ser Leu Leu Thr 1925 1930 1935 Glu Gln Glu Pro Trp Pro Glu Val Gly Arg Pro Arg Arg Ala Ala Val 1940 1945 1950 Ser Ser Phe Gly Leu Ser Gly Thr Asn Ala His Val Val Val Glu Glu 1955 1960 1965 Ala Pro Val Gly Glu Ala Gly Gln Ala Ala Gly Asp Ala Arg Leu Ala 1970 1975 1980 Val Val Pro Val Val Val Ser Gly Arg Ser Ala Gly Ala Val Ala Glu 1985 1990 1995 2000 Leu Ala Ser Arg Leu Asn Glu Ser Ile Arg Ser Asp Arg Leu Val Asp 2005 2010 2015 Val Gly Leu Ser Ser Val Val Ser Arg Ser Val Phe Glu His Arg Ser 2020 2025 2030 Val Leu Leu Ala Gly Asp Ser Gly Glu Leu His Thr Gly Leu Val Ala 2035 2040 2045 Val Gly Thr Gly Val Pro Ser Pro Gly Val Val Ser Gly Val Ala Ser 2050 2055 2060 Val Gly Gly Gly Arg Ser Val Phe Val Phe Pro Gly Gln Gly Thr Gln 2065 2070 2075 2080 Trp Ala Gly Met Ala Leu Gly Leu Trp Ala Glu Ser Ser Val Phe Ala 2085 2090 2095 Glu Ser Met Ala Arg Cys Glu Ala Ala Phe Glu Gly Leu Val Asp Trp 2100 2105 2110 Ser Leu Ala Asp Val Leu Gly Asp Gly Ser Ala Leu Glu Arg Val Asp 2115 2120 2125 Val Val Gln Pro Ala Ser Phe Ala Val Met Val Ser Leu Ala Glu Leu 2130 2135 2140 Trp Arg Ser Leu Gly Val Val Pro Asp Ala Val Val Gly His Ser Gln 2145 2150 2155 2160 Gly Glu Ile Ala Ala Ala Val Val Ala Gly Gly Leu Ser Leu Glu Asp 2165 2170 2175 Gly Ala Arg Val Val Val Leu Arg Ala Arg Leu Ile Gly Arg Glu Leu 2180 2185 2190 Ala Gly Arg Gly Gly Met Ala Ser Val Ala Leu Pro Val Ala Val Val 2195 2200 2205 Glu Glu Arg Leu Ala Gly Trp Ala Gly Arg Leu Gly Val Ala Val Val 2210 2215 2220 Asn Gly Pro Ser Ala Thr Val Val Ala Gly Asp Val Asp Ala Val Ala 2225 2230 2235 2240 Glu Phe Val Thr Ala Cys Glu Val Glu Gly Val Arg Ala Arg Val Leu 2245 2250 2255 Pro Val Asp Tyr Ala Ser His Ser Ala His Val Glu Asp Leu Lys Ala 2260 2265 2270 Glu Leu Glu Glu Val Leu Ala Gly Ile Gly Pro Val Thr Gly Gly Ile 2275 2280 2285 Pro Phe Tyr Ser Thr Ser Glu Ala Ala Gln Ile Asp Thr Ala Gly Leu 2290 2295 2300 Asp Ala Gly Tyr Trp Phe Gly Asn Leu Arg Arg Pro Val Arg Phe Gln 2305 2310 2315 2320 Glu Thr Val Glu Arg Leu Leu Ala Asp Gly Phe Arg Val Phe Val Glu 2325 2330 2335 Cys Gly Ala His Pro Val Leu Thr Gly Ala Val Gln Glu Thr Ala Glu 2340 2345 2350 Ser Thr Gly Arg Gln Val Cys Ala Val Gly Ser Leu Arg Arg Asp Glu 2355 2360 2365 Gly Gly Leu Arg Arg Phe Leu Thr Ser Ala Ala Glu Ala Phe Val Gln 2370 2375 2380 Gly Val Gly Val Phe Trp Pro Ala Leu Phe Asp Gly Thr Gly Ala Arg 2385 2390 2395 2400 Ile Val Asp Leu Pro Thr Tyr Pro Phe Gln Arg Arg His Tyr Trp Tyr 2405 2410 2415 Asn Asp Pro Ala Arg Arg Thr Gly Asp Ala Thr Ser Phe Gly Met Ala 2420 2425 2430 Gln Ala Gly His Pro Leu Leu Asp Ala Gly Thr Glu Leu Pro Glu Ser 2435 2440 2445 Gly Glu His Leu Tyr Thr Ala Arg Leu Ala Ala Asp Ser His Pro Trp 2450 2455 2460 Leu Leu Glu His Thr Leu Leu Gly Ala Pro Leu Leu Pro Gly Ala Ala 2465 2470 2475 2480 Phe Val Asp Leu Val Leu Trp Ala Gly Gly Glu Val Gly Cys Asp Leu 2485 2490 2495 Ile Glu Glu Leu Thr Leu Thr Ser Pro Leu Leu Leu Ser Asp Ser Ala 2500 2505 2510 Ala Leu Gln Leu Arg Leu Val Val Gly Thr Ala Asp Ala Glu Gly Arg 2515 2520 2525 Arg Thr Ile Thr Val His Ser Arg Pro Asp Gly Asp Pro Arg Thr Thr 2530 2535 2540 Arg Thr Pro Ala Ala Ser Ser Glu Thr Ser Pro Asp Ala Glu Ser Asp 2545 2550 2555 2560 Thr Glu Ile Arg Arg Asp Thr Ser Ala Trp Thr Lys His Ala Gln Ala 2565 2570 2575 Thr Val Ala Pro Ala Pro Asp Val Pro Pro Ser Gly Val Asp Ala Glu 2580 2585 2590 Gly Asp Ala Val Arg Pro Ala Val Glu Trp Ser Val Ala Ala Thr Glu 2595 2600 2605 Ser Asp Ala Phe Gln Ala Glu Asp Phe Tyr Ala Ser Phe Ala Ala His 2610 2615 2620 Gly Tyr Gly Tyr Gly Pro Leu Phe Gln Gly Val Arg Ser Gly Arg Gln 2625 2630 2635 2640 Asp Gly Thr Asp Val Tyr Ala Glu Val Ala Leu Asp His Asp Arg Leu 2645 2650 2655 Pro Ser Ala Glu Gln Phe Gly Leu His Pro Ala Leu Leu Asp Ala Ala 2660 2665 2670 Phe Gln Thr Met Arg Leu Gly Ser Phe Phe Pro Asp Asp Gly Gln Ala 2675 2680 2685 Arg Val Pro Tyr Thr Phe Arg Gly Ile Arg Leu Tyr Ala Pro Gly Ala 2690 2695 2700 Ala Arg Leu Arg Val Arg Val Ser Ala Val Gly Ala Asp Ala Val Arg 2705 2710 2715 2720 Val Glu Cys Ala Asp Glu Arg Gly Arg Leu Val Cys Glu Ile Asp Ala 2725 2730 2735 Leu Val Val Ser Thr Val Ser Pro Asp Gln Leu Arg Pro Ala Gly Gln 2740 2745 2750 Asp Ala Thr Gln Asp Met Leu His Arg Ile Glu Trp Pro Val Leu Ser 2755 2760 2765 Pro Pro Thr Gly Ser Ala Thr Ser Pro Ala Pro Pro Arg Trp Ile Val 2770 2775 2780 Val Gly Gly Glu Asp Glu Gly Leu Gly Leu Gly Gly Leu Arg Leu Asp 2785 2790 2795 2800 Gly Pro Arg Leu Asp Gly Pro Gly Leu Ala Glu Ala Leu Ser Glu Ala 2805 2810 2815 Gly Met Gly Thr Glu Arg His Arg Asn Leu Ala Asp Ala Leu Ser Ala 2820 2825 2830 Val Arg Thr Pro Val Asp Thr Ala Gly Ser Ala Ala Ala Ala Gly Thr 2835 2840 2845 Thr Ser Leu Ile Ala Val Pro Val Pro Gln Ser Pro Thr Met Asp Ala 2850 2855 2860 Gly Ala Val Arg His Ala Val His Arg Ala Leu Glu Leu Val Gln Gly 2865 2870 2875 2880 Trp Val Ala Ala Asp Glu Ala Ala Glu Glu Gly Gly Ser Asp Gly Ala 2885 2890 2895 Ala Ala Asp Arg Arg Leu Val Leu Val Thr Ser Gly Ala Val Ser Thr 2900 2905 2910 Gly Asp Ala Asp Pro Leu Arg Asp Pro Val Ala Ala Ala Val Trp Gly 2915 2920 2925 Leu Ile Lys Ser Ala Gln Ser Glu Gln Pro Gly Arg Ile Val Leu Val 2930 2935 2940 Asp Leu Asp Glu Gly Ala Val Asp Gly Ala Ala Leu Ala Ala Ala Ile 2945 2950 2955 2960 Ser Thr Gly Glu Pro Gln Leu Ala Leu Arg Asp Gly Asp Val His Val 2965 2970 2975 Pro Arg Leu Ala Pro Leu Ser Val Arg Asp Ser Gln Thr Leu Leu Pro 2980 2985 2990 Pro Ala Gly Thr Arg Ala Trp His Leu Val Gly Ala Gly Thr Gly Thr 2995 3000 3005 Leu Ser Asp Leu Ala Leu Val Pro Ala Gln Thr Asp Thr Val Ala Leu 3010 3015 3020 Ala Pro Gly Gln Val Arg Ile Ala Val Arg Ala Ala Gly Leu Asn Phe 3025 3030 3035 3040 Arg Asp Thr Leu Ile Ala Leu Gly Met Tyr Pro Gly Glu Gly Val Met 3045 3050 3055 Gly Ala Glu Gly Ala Gly Val Ile Thr Glu Val Gly Pro Asp Val Val 3060 3065 3070 Ser Leu Ala Val Gly Asp Arg Val Leu Gly Met Trp Thr Asp Gly Phe 3075 3080 3085 Gly Pro Tyr Val Val Ala Asp His Arg Met Val Ala Pro Met Pro Arg 3090 3095 3100 Asp Trp Ser Tyr Ala Glu Ala Ala Ser Val Pro Ala Val Phe Leu Ser 3105 3110 3115 3120 Ala Tyr Tyr Gly Leu Arg His Leu Ala Gly Leu Arg Ala Gly Gln Ser 3125 3130 3135 Val Leu Val His Ala Ala Ala Gly Gly Val Gly Met Ala Ala Val Gln 3140 3145 3150 Leu Ala Arg His Phe Gly Ala Glu Val Phe Gly Thr Ala Gly Thr Ala 3155 3160 3165 Lys Trp Asp Ala Leu Arg Ala Gln Gly Leu Asp Asp Arg His Ile Ala 3170 3175 3180 Gly Ser Arg Thr Leu Asp Phe Ala Asp Arg Phe Leu Asp Ala Thr Glu 3185 3190 3195 3200 Gly Arg Gly Val Asp Val Val Leu Asn Ser Leu Ala Gly Asp Phe Val 3205 3210 3215 Asp Ala Ser Leu Arg Leu Leu Pro Arg Gly Gly Arg Phe Val Glu Leu 3220 3225 3230 Gly Lys Ala Asp Val Arg Asp Ala Ala Gln Val Ala Ala Asp Arg Pro 3235 3240 3245 Gly Thr Val Tyr Arg Ala Phe Glu Leu Met Glu Ala Gly Pro Glu Leu 3250 3255 3260 Ile Gly Arg Met Leu Asn Glu Leu Leu Glu Leu Phe Glu Ser Gly Ala 3265 3270 3275 3280 Leu Arg Leu Leu Pro Val Thr Pro Tyr Asp Ile Arg Arg Ala Pro Asp 3285 3290 3295 Ala Phe Arg Thr Leu Ser Gln Ala Gly His Val Gly Lys Leu Val Leu 3300 3305 3310 Thr Met Pro Pro Ala Phe Glu Pro His Gly Thr Val Leu Ile Thr Gly 3315 3320 3325 Gly Thr Gly Asn Leu Gly Gly Thr Leu Ala Arg His Leu Val Thr Glu 3330 3335 3340 His Gly Val Arg His Leu Leu Leu Ala Gly Arg Arg Gly Pro Glu Ala 3345 3350 3355 3360 Glu Gly Ala Ala Glu Leu Val Arg Glu Leu His Asp Leu Gly Ala Ser 3365 3370 3375 Val Thr Val Ala Ala Cys Asp Val Ala Asp Arg Ala Ala Leu Arg Lys 3380 3385 3390 Leu Leu Gly Gly Ile Pro Pro Glu Arg Pro Leu Thr Gly Val Val His 3395 3400 3405 Ala Ala Gly Val Leu Asp Asp Gly Val Val Thr Ser Leu Thr Pro Asp 3410 3415 3420 Arg Val Asp Gly Val Leu Arg Pro Lys Val Asp Ala Ala Leu Asn Leu 3425 3430 3435 3440 His Glu Ala Ala Leu Asp Pro Glu Leu Gly Leu Asp Ile Thr Ala Phe 3445 3450 3455 Val Leu Phe Ser Ser Val Ala Ala Leu Leu Gly Gly Ser Gly Gln Gly 3460 3465 3470 Ser Tyr Ala Ala Ala Asn Gly Phe Leu Asp Gly Leu Ala Gln Tyr Arg 3475 3480 3485 Arg Gly Arg Ser Leu Pro Ala Leu Ser Leu Gly Trp Gly Leu Ala Gly 3490 3495 3500 Ser Gly Arg Met Thr Ser His Leu Asp Ser Arg Ala Leu Leu Arg Arg 3505 3510 3515 3520 Met Ala Arg Gly Gly Val Leu Pro Leu Ser Pro Ala Glu Ser Met Ala 3525 3530 3535 Leu Phe Asp Ala Ala Gln Gly Phe Asp Glu Ala Leu Gln Val Pro Ala 3540 3545 3550 Arg Phe His Thr Ala Ala Leu Gly Ala Asp Gly Asn Val Pro Pro Leu 3555 3560 3565 Phe Asn Gly Leu Ile Arg Gly Gly Thr Ala His Ala Glu Ala Arg Arg 3570 3575 3580 Arg Thr Val Gly Ala Ser Pro Ala Gly Gly Pro Ala Gly Gly Glu Pro 3585 3590 3595 3600 Val Asn Leu Ala Asp Arg Leu Ser Gly Leu Thr Glu Asp Glu Gln Arg 3605 3610 3615 Ala Leu Leu Leu Asp Thr Val Arg Thr His Ala Ala Leu Val Leu Gly 3620 3625 3630 His Thr Gly Thr Asp Gly Ile Gln Ala Asp Arg Ala Phe Lys Asp Leu 3635 3640 3645 Gly Phe Asp Ser Leu Thr Ala Val Glu Met Arg Asn Arg Leu Thr Ala 3650 3655 3660 Ala Thr Gly Leu His Leu Ala Ala Thr Leu Val Phe Asp His Pro Ala 3665 3670 3675 3680 Pro Ala Asp Leu Ala Glu His Leu Arg Ser Arg Leu Val Pro Glu Gly 3685 3690 3695 Thr Asp Val Pro Pro Leu Leu Ala Glu Leu Gly Arg Leu Glu Thr Ala 3700 3705 3710 Phe Lys Lys Leu Thr Thr Ala Asp Leu Ala Ser Val Val Pro Asp Asp 3715 3720 3725 Ile Ala Arg Asp Glu Ile Ala Val Arg Leu Ala Ala Leu Gly Ser Leu 3730 3735 3740 Trp Asn Gly Leu His Gly Asn Gly Leu Ser Gly Asp Ala Ala Gln Lys 3745 3750 3755 3760 His Gly Asp Ser Ile Val Glu Asp Ile Asp Ser Ala Asp Asp Asp Glu 3765 3770 3775 Ile Phe Ala Phe Leu Asp Glu Ser Phe Gly Asp Ser 3780 3785 26 1612 PRT Streptomyces bikiniensis 26 Met Ala Thr Glu His Glu Gln Lys Leu Arg Asp Tyr Leu Lys Arg Ala 1 5 10 15 Thr Thr Glu Leu His Lys Ala Thr Glu Arg Leu Lys Glu Val Glu Gln 20 25 30 Arg Ala His Glu Pro Val Ala Ile Val Gly Met Gly Cys Arg Phe Pro 35 40 45 Gly Gly Ala Ser Ser Pro Glu Glu Leu Trp Asp Leu Val Ala Ala Glu 50 55 60 Thr Asp Ala Val Ser Pro Phe Pro Val Asp Arg Gly Trp Asp Val Thr 65 70 75 80 Gly Leu Tyr Asp Pro Asp Pro Asp Ala Ala Gly Arg Ala Tyr Val Arg 85 90 95 Glu Gly Gly Phe Leu His Asp Ala Gly Glu Phe Asp Ala Gly Phe Phe 100 105 110 Gly Ile Ser Pro Arg Glu Ala Leu Ala Met Asp Pro Gln Gln Arg Leu 115 120 125 Leu Leu Glu Thr Ser Trp Glu Ala Leu Glu Arg Ala Gly Ile Asp Pro 130 135 140 His Thr Leu Arg Gly Thr Arg Thr Gly Val Tyr Met Gly Ala Trp Asn 145 150 155 160 Gly Gly Tyr Ala Glu Gly Ile Pro Gln Pro Thr Ala Glu Leu Glu Ala 165 170 175 Gln Leu Leu Thr Gly Gly Val Val Ser Phe Thr Ser Gly Arg Val Ser 180 185 190 Tyr Leu Leu Gly Leu Glu Gly Pro Ala Val Thr Val Asp Thr Ala Cys 195 200 205 Ser Ser Ser Leu Val Ala Leu His Leu Ala Val Arg Ala Leu Arg Ser 210 215 220 Gly Glu Cys Asp Leu Ala Leu Ala Gly Gly Ala Thr Val Met Ser Thr 225 230 235 240 Pro Asp Val Phe Val Arg Phe Ser Arg Gln Arg Gly Val Ala Ala Asp 245 250 255 Gly Arg Cys Lys Ala Phe Ser Ala Ser Ala Asp Gly Phe Gly Pro Ala 260 265 270 Glu Gly Val Gly Val Leu Ala Val Glu Arg Leu Ser Asp Ala Val Arg 275 280 285 His Gly Arg Arg Val Leu Ala Val Val Arg Gly Ser Ala Val Asn Gln 290 295 300 Asp Gly Ala Ser Asn Gly Leu Thr Ala Pro Ser Gly Arg Ala Gln Ala 305 310 315 320 Leu Leu Ile Arg Arg Ala Leu Ala Asp Ala Arg Leu Gly Val Ala Asp 325 330 335 Val Asp Val Val Glu Gly His Gly Thr Gly Thr Arg Leu Gly Asp Pro 340 345 350 Ile Glu Ala Gln Ala Leu Leu Ala Thr Tyr Gly Gln Arg Asp Ala Gly 355 360 365 Arg Pro Leu Arg Leu Gly Ser Leu Lys Ser Asn Val Gly His Thr Gln 370 375 380 Ala Ala Ala Gly Val Ala Gly Val Ile Lys Met Val Met Ala Met Arg 385 390 395 400 His Gly Val Leu Pro Lys Thr Leu His Val Asp Glu Pro Thr Ala Glu 405 410 415 Val Asp Trp Ser Ala Gly Ala Val Ser Leu Leu Arg Glu Gln Glu Ala 420 425 430 Trp Pro Glu Val Gly Arg Leu Arg Arg Ala Ala Val Ser Ser Phe Gly 435 440 445 Val Ser Gly Thr Asn Ala His Val Val Val Glu Glu Ala Pro Val Pro 450 455 460 Glu Asp Gly Glu Ala Val Gly Gly Gly Val Pro Leu Ala Val Val Pro 465 470 475 480 Val Val Val Ser Gly Arg Ser Ala Gly Ala Val Ala Glu Leu Ala Gly 485 490 495 Arg Val Ser Glu Val Ala Ala Ser Gly Arg Leu Val Asp Val Gly Leu 500 505 510 Ser Ser Val Val Ser Arg Ser Val Phe Glu His Arg Ser Val Val Leu 515 520 525 Ala Gly Asp Ser Ala Glu Leu Asn Ala Gly Leu Asp Ala Val Ala Gly 530 535 540 Gly Val Pro Ser Pro Gly Val Val Ser Gly Val Ala Ser Gly Glu Gly 545 550 555 560 Gly Arg Ser Val Phe Val Phe Pro Gly Gln Gly Thr Gln Trp Ala Gly 565 570 575 Met Ala Leu Gly Leu Trp Ala Glu Ser Ser Val Phe Ala Glu Ser Met 580 585 590 Ala Arg Cys Glu Ala Ala Phe Val Gly Leu Val Asp Trp Arg Leu Ser 595 600 605 Gln Val Leu Ser Asp Gly Ser Ala Leu Glu Arg Val Glu Val Val Gln 610 615 620 Pro Ala Ser Phe Ala Val Met Val Ser Leu Ala Glu Leu Trp Arg Ser 625 630 635 640 Leu Gly Val Val Pro Asp Ala Val Val Gly His Ser Gln Gly Glu Ile 645 650 655 Ala Ala Ala Val Val Ala Gly Gly Leu Ser Leu Glu Asp Gly Ala Arg 660 665 670 Val Val Val Leu Arg Ala Arg Leu Ile Gly Arg Glu Leu Ala Gly Arg 675 680 685 Gly Gly Met Ala Ser Val Ala Leu Pro Val Ala Val Val Glu Glu Arg 690 695 700 Leu Ala Gly Trp Ala Gly Arg Leu Gly Val Ala Val Val Asn Gly Pro 705 710 715 720 Ser Ala Thr Val Val Ala Gly Asp Val Asp Ala Val Ala Glu Phe Val 725 730 735 Ala Ala Cys Glu Val Glu Gly Val Arg Ala Arg Val Leu Pro Val Asp 740 745 750 Tyr Ala Ser His Ser Ala His Val Glu Asp Leu Lys Ala Glu Leu Glu 755 760 765 Gln Ile Leu Ala Gly Ile Gly Pro Val Thr Gly Gly Ile Pro Phe Tyr 770 775 780 Ser Thr Ser Glu Ala Ala Gln Ile Asp Thr Ala Gly Leu Asp Ala Gly 785 790 795 800 Tyr Trp Phe Gly Asn Leu Arg Arg Pro Val Arg Phe Gln Glu Thr Val 805 810 815 Glu Arg Leu Leu Ala Asp Gly Phe Arg Val Phe Val Glu Cys Gly Ala 820 825 830 His Pro Val Leu Thr Gly Ala Val Gln Glu Thr Ala Glu Ser Thr Gly 835 840 845 Arg Gln Val Cys Ala Val Gly Ser Leu Arg Arg Asp Glu Gly Gly Leu 850 855 860 Arg Arg Phe Leu Thr Ser Ala Ala Glu Ala Phe Val Gln Gly Val Glu 865 870 875 880 Val Ser Trp Pro Ala Leu Phe Glu Gly Thr Gly Ala Arg Thr Val Asp 885 890 895 Leu Pro Thr Tyr Pro Phe Gln Arg Arg Arg Tyr Trp Leu Glu Ser Arg 900 905 910 Pro Pro Ala Ala Pro Ile Glu Thr Ala Ala Ala Ser Gly Ile Glu Ser 915 920 925 Trp Arg Tyr Arg Val Ala Trp Lys Ser Leu Ser Leu Ser Glu Ser Ser 930 935 940 Arg Leu Asp Gly Arg Trp Leu Leu Val Val Pro Glu Thr Leu Asp Ala 945 950 955 960 Asp Gly Thr Arg Ile Ala His Asp Ile Gln His Ala Leu Thr Thr His 965 970 975 Gly Ala Thr Val Ser Arg Leu Thr Val Asp Val Thr Thr Thr Asp Arg 980 985 990 Ala Asp Leu Ser Ala Arg Leu Thr Thr Thr Ala Ala Glu Asp Gln Gly 995 1000 1005 Pro Leu Arg Gly Val Leu Ser Leu Leu Ser Thr Asp Glu Arg Gln His 1010 1015 1020 Pro Asp His Pro Gly Val Asp Arg Ala Thr Ala Gly Thr Met Leu Leu 1025 1030 1035 1040 Ala Gln Ala Cys Gly Asp Leu Val Val Ala Arg Gly Val Glu Pro Arg 1045 1050 1055 Leu Trp Val Val Thr Arg Gly Ala Val Ala Val Ser Pro Ala Glu Arg 1060 1065 1070 Pro Ser Ser Ala Gly Ala Gln Val Trp Gly Leu Gly Arg Cys Ala Ala 1075 1080 1085 Leu Glu Leu Pro Thr Arg Trp Gly Gly Met Val Asp Leu Pro Pro Ala 1090 1095 1100 Ala Arg Asp Ala Gly Arg His Val Arg Arg Leu Val Arg Leu Leu Ser 1105 1110 1115 1120 Glu Thr Cys Ala Glu Asp Gln Val Ala Leu Arg Ala Ser Gly Ala Tyr 1125 1130 1135 Gly Arg Arg Leu Leu Pro Ala Ser Ser Pro Ser Val Ser Val Pro Arg 1140 1145 1150 Thr Ala Lys Ser Gly Tyr Gln Pro Arg Gly Thr Val Leu Val Thr Gly 1155 1160 1165 Gly Thr Gly Ala Leu Gly Gly His Leu Ala Arg Trp Leu Ala Arg Asn 1170 1175 1180 Gly Ala Glu His Ile Val Leu Ala Gly Arg Arg Gly Glu Gly Ala Pro 1185 1190 1195 1200 Gly Ala Ala Glu Leu Ser Ala Glu Leu Lys Glu Leu Gly Ala Glu Val 1205 1210 1215 Thr Val Ala Ala Cys Asp Val Ala Asp Arg Asn Ala Leu Arg Asp Met 1220 1225 1230 Leu Glu Ser Leu Pro Ala Asp Arg Pro Leu Ser Gly Val Phe His Ala 1235 1240 1245 Ala Gly Val Pro His Ser Ala Pro Leu Ala Glu Thr Asp Val Ala Gly 1250 1255 1260 Leu Ala Ala Val Leu Pro Gly Lys Val Val Gly Ala Arg His Leu His 1265 1270 1275 1280 Glu Leu Thr Arg Glu Lys Glu Leu Asp Ala Phe Val Leu Tyr Ala Ser 1285 1290 1295 Gly Ala Gly Val Trp Gly Ser Gly Gly Gln Ser Ala Tyr Gly Ala Ala 1300 1305 1310 Asn Ala Ala Leu Asp Ala Leu Ala Glu Gln Arg Arg Ala Glu Gly Leu 1315 1320 1325 Pro Ala Thr Ser Val Ser Trp Gly Leu Trp Asp Gly Gly Gly Met Ala 1330 1335 1340 Gly Glu Arg Gly Glu Glu Phe Leu Thr Ala Leu Gly Leu Arg Ala Met 1345 1350 1355 1360 Glu Pro Glu Ser Ala Val Ala Ala Leu Glu Glu Ala Leu Asp Arg Gly 1365 1370 1375 Asp Thr Cys Val Ser Val Val Asp Val Asp Trp Ser Arg Phe Ala Glu 1380 1385 1390 Ser Phe Thr Ala Phe Arg Pro Ser Pro Leu Ile Gly Glu Leu Pro Gly 1395 1400 1405 Val Arg Ala Val Pro Asp Gly Ser Ala Gly Gly Pro Ser Asp Asp Leu 1410 1415 1420 Ala Asp Ala Ala Arg His Gly Gly Ala Ala Asp Arg Gly Val Pro Ala 1425 1430 1435 1440 Gly Leu Ala Arg Ala Thr Gly Asp Asp Arg Gln Asp Ile Leu Leu Asp 1445 1450 1455 Leu Val Arg Arg His Ala Ala Ala Val Leu Gly His Pro Gly Pro Gln 1460 1465 1470 His Ile Glu Pro Asp Ala Gly Phe Arg Thr Leu Gly Phe Ser Ser Val 1475 1480 1485 Thr Ala Val Glu Leu Ala Asn Lys Leu Gly Ala Ala Val Gly Thr Lys 1490 1495 1500 Ile Pro Ala Thr Phe Ala Phe Asp His Pro Asn Ala Arg Ala Ala Ala 1505 1510 1515 1520 Ser Arg Leu Asp Val Leu Leu Ala Ala Ser Ser Asp Glu Thr Ala Gln 1525 1530 1535 Glu Ala Glu Ile Arg Gln Ala Leu Arg Thr Val Pro Leu Ala Arg Leu 1540 1545 1550 Arg Ala Ala Gly Leu Leu Asp Gly Leu Leu Glu Leu Ala Gly Leu Glu 1555 1560 1565 Ala Glu Pro Gly Leu Pro Gly Asp Val Pro Asp Arg Gly Ala Ala Thr 1570 1575 1580 Pro Asp Glu Glu Ser Ala Leu Ala Glu Val Asp Gly Leu Asp Ala Glu 1585 1590 1595 1600 Ala Leu Val Asp Leu Val Leu Asn Gln Ser Asp Ser 1605 1610 27 1350 PRT Streptomyces bikiniensis 27 Met Ala Leu Ser Gln Glu Lys Val Leu Glu Ala Leu Arg Thr Ser Val 1 5 10 15 Lys Asp Ala Glu Arg Leu Arg Lys Arg Asn Arg Glu Leu Leu Ala Ala 20 25 30 Arg His Glu Pro Ile Ala Val Val Gly Met Ala Cys Arg Tyr Pro Gly 35 40 45 Gly Val Arg Ser Pro Glu Asp Leu Trp Glu Leu Val Val Ser Gly Thr 50 55 60 Asp Ala Val Gly Pro Phe Pro Glu Asp Arg Gly Trp Asp Val Glu Arg 65 70 75 80 Ile Tyr Asp Gln Asp Pro Ser Val Pro Gly Thr Thr Tyr Cys Arg Glu 85 90 95 Gly Gly Phe Leu Tyr Asp Ala Gly Asp Phe Asp Ala Ala Phe Phe Gly 100 105 110 Ile Gly Pro Arg Glu Ala Thr Val Met Asp Pro Gln Gln Arg Gln Leu 115 120 125 Leu Glu Ala Ser Trp Glu Ala Leu Glu Gln Ala Gly Leu Asp Pro Arg 130 135 140 Ala Leu Arg Gly Ser Gln Gly Gly Val Phe Val Gly Ala Ala Asn Gln 145 150 155 160 Gly Tyr Val Pro Gly Asp Ala Ala Ala Ser Gly Arg Leu Pro Glu Gly 165 170 175 Ser Asp Gly Tyr Leu Leu Thr Gly Asn Ala Asp Ala Val Leu Ser Gly 180 185 190 Arg Ile Ser Tyr Phe Leu Gly Leu Glu Gly Pro Ser Met Thr Val Glu 195 200 205 Thr Ala Cys Ser Ser Ser Leu Val Ala Leu His Leu Ala Val Gln Ala 210 215 220 Leu Arg Arg Glu Glu Cys Glu Phe Ala Leu Ala Gly Gly Val Ala Val 225 230 235 240 Leu Ala Asn Pro Ala Ala Tyr Val Glu Phe Ala Arg Gln Arg Gly Leu 245 250 255 Ala Pro Asp Gly Arg Cys Lys Ala Phe Asp Asp Ala Ala Asp Gly Thr 260 265 270 Gly Trp Ala Glu Gly Val Gly Val Leu Val Val Glu Arg Leu Ser Asp 275 280 285 Ala Val Arg Lys Gly His Arg Val Leu Ala Val Val Arg Gly Thr Ala 290 295 300 Val Asn Gln Asp Gly Ala Ser Ser Gly Leu Ser Val Pro Asn Gly Pro 305 310 315 320 Ser Gln Gln Arg Val Ile Arg Arg Ala Leu Ala Asp Ala Arg Leu Glu 325 330 335 Ala Gly Gln Ile Asp Ala Val Glu Ala His Gly Thr Gly Thr Arg Leu 340 345 350 Gly Asp Pro Ile Glu Ala Gln Ala Leu Leu Asp Thr Tyr Gly Glu Glu 355 360 365 Arg Ser Pro Glu Arg Pro Leu Trp Val Gly Ser Leu Lys Ser Asn Phe 370 375 380 Gly His Ala Gln Ala Ala Ala Gly Val Gly Gly Val Ile Lys Thr Val 385 390 395 400 Met Ala Leu Arg His Gly Leu Leu Pro Arg Thr Leu His Val Thr Ser 405 410 415 Pro Thr Arg His Val Asp Trp Gly Asp Gly Gln Val Arg Leu Leu Thr 420 425 430 Glu Pro Val Asp Trp Pro Arg Thr Gly Ala Pro Arg Arg Ala Ala Val 435 440 445 Ser Ala Phe Gly Val Ser Gly Thr Asn Gly His Ile Ile Leu Glu Glu 450 455 460 Ala Pro Pro Pro Thr Arg Pro Glu Ala Val Arg Gln Ala Gly Glu Arg 465 470 475 480 Arg Pro Val Leu Val Pro Trp Thr Leu Ser Gly Arg Thr Arg Pro Ala 485 490 495 Leu Cys Arg Gln Ala Ala Arg Leu Ala Ala His Leu Glu Gln His Pro 500 505 510 Asp Leu Asp Pro Leu Asp Val Gly Phe Ser Leu Ala Thr Thr Arg Thr 515 520 525 His Phe Glu His Arg Ala Val Leu Leu Ala Asp Ala Ala Thr Glu Gly 530 535 540 Gly Ser Arg Ala Asp Ala Leu Gly Ala Leu Arg Ala Ile Ala Glu Asp 545 550 555 560 Arg Asp Pro Gly Gly Ala Val Arg Asp Thr Ala Arg Gly Glu Gly Arg 565 570 575 Ile Ala Phe Leu Phe Cys Gly Gln Gly Ser Gln Arg Pro Gly Met Ala 580 585 590 Glu Gln Leu Tyr Ala Gln Tyr Pro Ala Phe Ala Arg Glu Leu Asp Thr 595 600 605 Ile Ala Thr His Leu Asp Ala His Leu Asp Arg Pro Leu Ala Thr Val 610 615 620 Met Phe Ala Pro Ala Gly Thr Ala Glu Ala Ala Leu Leu Asp Gly Thr 625 630 635 640 Gln Tyr Ala Gln Ala Ala Leu Phe Ala Val Glu Val Ala Leu Phe Arg 645 650 655 Leu Phe Glu Gly Trp Gly Leu Arg Pro Asp Val Leu Leu Gly His Ser 660 665 670 Val Gly Glu Leu Ala Ala Ala His Val Ala Gly Val Phe Gly Pro Ala 675 680 685 Asp Ala Cys Ser Leu Val Ala Ala Arg Gly Arg Leu Met Gln Glu Leu 690 695 700 Pro Ala Gly Gly Ala Met Leu Ser Val Arg Ala Ala Glu His Glu Val 705 710 715 720 Arg Glu Leu Ile Ala Gly Gln Glu Asp Arg Ile Ala Val Ala Ala Val 725 730 735 Asn Gly Pro Arg Ser Val Val Val Ser Gly Asp Glu Asp Ala Val Ser 740 745 750 Ala Leu Ala Glu Glu Leu Thr Glu Tyr Gly Val Arg Thr Lys Arg Leu 755 760 765 Asn Val Ser His Ala Phe His Ser Pro Arg Leu Asp Ser Met Leu Glu 770 775 780 Thr Phe Arg Arg Val Ala Glu Thr Val Glu Tyr Arg Glu Pro Thr Leu 785 790 795 800 Asp Val Ile Ser Gly Leu Thr Gly Arg Pro Ala Asp Ala Gly Glu Leu 805 810 815 Ala Thr Ala Asp Tyr Trp Val Arg Gln Ala Arg Glu Thr Val Arg Phe 820 825 830 His Asp Gly Val Arg Ala Ala His Ala Arg Gly Val Ser Thr Phe Val 835 840 845 Glu Leu Gly Pro Asp Gly Val Leu Cys Gly Leu Ala Leu Glu Thr Leu 850 855 860 Ala Glu Glu Thr Asp Gly Glu Ala Ala Ala Glu Thr Pro Gly Arg Ala 865 870 875 880 Arg Ala Ala Leu Val Pro Val Met Arg Arg Glu Arg Pro Glu Gly Ser 885 890 895 Thr Leu Leu Thr Ala Leu Ala Thr Ala His Ala Arg Gly Ala Glu Val 900 905 910 Asp Trp Ser Arg Phe Tyr Ala Asp Thr Gly Ala Arg His Thr Thr Leu 915 920 925 Pro Thr Tyr Ala Phe Gln Arg Gln Arg Phe Trp Leu Glu Thr Ala Ala 930 935 940 Pro Ala Ala Pro Ala Ala Gly Gln Gly Ala Gly Pro Ala Asp Pro Gln 945 950 955 960 Asp Ser Thr Gly Pro Ala Ala Arg Pro Thr Leu Thr Glu Gln Asp Leu 965 970 975 Leu Leu Leu Val Arg Thr Glu Ala Ala Ala Ala Leu Gly His Ala Glu 980 985 990 Leu Glu Asp Val Pro Ala Asp Ser Leu Phe Gly Asp Ile Gly Phe Asp 995 1000 1005 Ser Leu Ala Ala Ile Glu Leu Gly Ala Ala Leu Thr Gly Ala Thr Gly 1010 1015 1020 Leu Glu Val Pro Ser Ser Leu Val Leu Asp His Pro Thr Pro Arg Glu 1025 1030 1035 1040 Leu Ala Ala His Leu Ala Ala Ala Arg Thr Ala Ala Asp Ser Asp Asp 1045 1050 1055 Thr Ser Pro Glu Gly Pro Asp Thr Ala Gly Glu Ser Ser Leu Ser Ala 1060 1065 1070 Met Tyr Arg Arg Ala Val Arg Leu Gly Arg Ala Glu Pro Phe Ile Gly 1075 1080 1085 Thr Leu Ala Glu Leu Ala Ala Phe Arg Pro Val Phe Pro Ala Asp His 1090 1095 1100 Thr Leu Ala Asp Gly Glu Thr Val Gly Gln Ala Ala Ala Ala Trp Gln 1105 1110 1115 1120 Pro Ala Pro Val Arg Leu Ala Thr Thr Asp Gly Glu Gly Pro Glu Leu 1125 1130 1135 Ile Cys Cys Ala Gly Thr Ala Val Ala Ser Gly Pro Glu Glu Phe Thr 1140 1145 1150 Ala Leu Ala Ala Ala Leu Gly Asp Arg Leu Thr Val Ser Ala Leu Arg 1155 1160 1165 Gln Pro Gly Phe Arg Ala Asn Glu Leu Leu Pro Gly Ser Leu Asp Gly 1170 1175 1180 Leu Leu Asp Ala Gln Ala Asp Ala Val Leu Arg His Thr Gly Asp Arg 1185 1190 1195 1200 Pro Tyr Ala Leu Leu Gly His Ser Ala Gly Gly Ala Leu Ala His Ala 1205 1210 1215 Leu Ala Cys Arg Leu Glu Glu Leu Gly Ala Gly Pro Ala Ala Leu Val 1220 1225 1230 Leu Ala Asp Val Tyr Leu Pro Ser Ser Pro Gly Ala Met Gly Val Trp 1235 1240 1245 Arg Asn Glu Met Leu Asp Trp Val Met Arg Arg Ser Val Val Ser Ile 1250 1255 1260 Asp Asp Ala Arg Leu Thr Ala Met Gly Ala Tyr Asn Gln Met Leu Leu 1265 1270 1275 1280 Glu Trp Thr Pro Arg Pro Thr Lys Ala Pro Val Leu Phe Leu Arg Ala 1285 1290 1295 Thr Glu Pro Val Arg Pro Trp Ser Gly Glu Pro Glu Ser Trp Arg Ala 1300 1305 1310 His Trp Asp Gly Gly Asp His Thr Ala Val Asp Val Pro Gly Thr His 1315 1320 1325 Leu Thr Leu Met Thr Glu His Ala Arg His Leu Ala Ala Thr Leu His 1330 1335 1340 Thr Trp Leu Gly Thr Leu 1345 1350 28 412 PRT Streptomyces bikiniensis 28 Val Thr Thr Gln Trp Thr Thr Pro Ser Val Leu Gly Arg Arg Leu Gln 1 5 10 15 Arg Thr Tyr Val Gly His Trp Phe Ala Gly Thr Gln Gly Asp Pro Tyr 20 25 30 Ala Leu Ile Leu Arg Ala Gln Arg Asp Asp Thr Thr Pro Tyr Glu Glu 35 40 45 Asp Val Arg Ala Arg Gly Pro Val Phe His Ser Glu Val Leu Asp Thr 50 55 60 Trp Val Ile Thr Asp Gly Ala Leu Ala Arg Ser Val Leu Thr Asp Ala 65 70 75 80 Arg Phe Gly Gly Leu Thr Arg Ala Gly Gly Arg Tyr Arg Ala Glu Leu 85 90 95 Leu Pro Pro Ala Gly Pro Glu Val Gly Pro Ala Arg Ala Gly Val Arg 100 105 110 Gly Gly Val Arg Ala Asp Ala Asp Pro Ala Val Ser Ala Gln Asp Glu 115 120 125 Val Val Val Glu Ala Leu Ala Glu Gln Leu Ser Arg Thr Leu Leu Gly 130 135 140 Gly Leu Gly Asp Asp Phe Asp Leu Val Ala Ala Phe Ala Arg Arg Leu 145 150 155 160 Pro Ala Gln Val Leu Ala Glu Phe Leu Gly Leu Pro Ala Ala Ala Arg 165 170 175 Ser Arg Phe Glu Glu Leu Leu Ala Gly Cys Ala His Ser Leu Asp Ser 180 185 190 Arg Leu Cys Pro Gln Thr Leu Asp Ile Thr Arg Thr Gly Leu Gly Ala 195 200 205 Ala Ala Glu Leu Arg Glu Leu Leu Ala Arg His Leu Gly Gly Ser Gly 210 215 220 Pro Arg Ser Ala Gln Ala Ala Val Ser Leu Ala Val Glu Val Ala Ala 225 230 235 240 Pro Ala Gly Ala Leu Ile Cys Asn Ala Val Glu Ala Leu Ser Ser Ser 245 250 255 Pro Gly Gln Trp Asn Ala Leu Arg Gln Asn Pro Glu Lys Ala Asp Ala 260 265 270 Val Val Ala Glu Thr Trp Trp Arg Arg Pro Pro Val Arg Val Glu Ser 275 280 285 Arg Ile Ala Gln Glu Asp Val Asp Val Ala Gly Val Pro Val Pro Ala 290 295 300 Asp Gly His Val Ala Ile Leu Val Ala Ala Ala Gln Arg Asp Pro Ala 305 310 315 320 Ile Thr Pro Ala Pro Thr Lys Asp Asp Thr Gly Thr Pro Gly Gln Gly 325 330 335 Asp Cys Gly Val Pro Leu Gly Leu Val Gly Asp Ala His Ala Thr Ser 340 345 350 Ala Ala Arg Thr Val Arg Ala Leu Cys Arg Gly Ala Leu Arg Ala Leu 355 360 365 Ala Gln Glu Ala Pro Gly Leu Arg Pro Asn Gly Thr Pro Val Arg Leu 370 375 380 Arg Arg Ala Pro Val Thr Leu Gly His Ala Arg Phe Pro Val Ala Arg 385 390 395 400 Thr Gly Arg Gly Thr Pro Thr Asp Ala Gly Ala Ala 405 410 29 425 PRT Streptomyces bikiniensis 29 Met Arg Val Leu Met Thr Ser Ile Ala His Asn Thr His Tyr Tyr His 1 5 10 15 Leu Val Pro Leu Ala Trp Ala Leu Lys Ala Ala Gly His Glu Val Arg 20 25 30 Val Ala Gly Gln Pro Arg Val Thr Asp Ile Ile Thr Gly Ser Gly Leu 35 40 45 Thr Ala Val Pro Val Gly Asp Asp Glu Asp Met Met Glu Leu Phe Ala 50 55 60 Glu Ile Gly Gly Asp Ile Thr Pro Tyr Gln Glu Gly Leu Asp Phe Ala 65 70 75 80 Glu Glu Arg Pro Glu Ala Arg Ser Trp Glu His Leu Leu Gly Gln Gln 85 90 95 Thr Val Leu Thr Ser Leu Cys Phe Ala Pro Leu Asn Gly Asp Ser Thr 100 105 110 Met Asp Asp Ile Val Ala Leu Ala Arg Ser Trp Gln Pro Asp Leu Val 115 120 125 Ile Trp Glu Pro Phe Thr Phe Ala Gly Ala Val Ala Ala His Ala Val 130 135 140 Gly Ala Ala His Ala Arg Val Leu Trp Gly Pro Asp Val Ile Gly Arg 145 150 155 160 Ala Arg Glu Arg Phe Val Glu Ala Lys Ala Gln Gln Ala Pro Glu His 165 170 175 Arg Glu Asp Pro Met Ala Glu Trp Leu Gly Trp Thr Leu Glu Arg Leu 180 185 190 Gly Leu Pro Ala Ala Gly Asp Gly Met Glu Glu Leu Leu Asn Gly Gln 195 200 205 Trp Val Ile Asp Pro Gly Pro Glu Ser Val Arg Leu Asp Leu Arg Glu 210 215 220 Pro Ile Leu Pro Met Arg Phe Val Pro Tyr Asn Gly Pro Ala Val Val 225 230 235 240 Pro Gly Trp Leu Ser Glu Lys Pro Lys Arg Pro Arg Val Cys Leu Thr 245 250 255 Gln Gly Val Ser Gly Arg Glu Thr His Gly Lys Asp Ala Val Arg Phe 260 265 270 Gln Asp Leu Leu Ala Ala Leu Gly Asp Leu Asp Ile Glu Ile Val Ala 275 280 285 Thr Leu Asp Ser Thr Gln Arg Glu Asn Leu Thr Glu Val Pro Asp Asn 290 295 300 Val Arg Ile Val Asp Phe Val Ser Met Asp Val Leu Leu Pro Ser Cys 305 310 315 320 Ala Met Ile Ile Tyr His Gly Gly Ala Gly Thr Ser Ala Thr Ala Leu 325 330 335 Leu His Gly Val Pro Gln Val Val Ile Gly Ala His Trp Asp Val Pro 340 345 350 Val Arg Ala Arg Gln Leu Asp Asp Leu Gly Ala Gly Ile Phe Ile Arg 355 360 365 Pro Glu Asp Leu Asp Ala Ala Thr Leu Arg Ala Ala Val Gln Arg Val 370 375 380 Leu Thr Glu Pro Ser Leu Gln Arg Ala Ala Asp Arg Leu Arg Ala Glu 385 390 395 400 Met Arg Ser Asn Pro Thr Pro Ala Glu Thr Val Thr Val Leu Glu Arg 405 410 415 Leu Ser Arg Ser His Arg Gln Pro Arg 420 425 30 248 PRT Streptomyces bikiniensis 30 Met Glu Phe Glu Gly Gln Val Ala Leu Val Thr Gly Ala Gly Arg Gly 1 5 10 15 Ile Gly Arg Ala Thr Val Val Arg Leu Ala Glu Ala Gly Cys Asp Ile 20 25 30 Ala Leu His Tyr Asn Gln Ala Lys Ala Gln Ala Glu Glu Val Ala Glu 35 40 45 Arg Ile Ala Ala Leu Gly Arg Thr Val Glu Leu Phe Pro Gly Asp Leu 50 55 60 Ser Arg Pro Glu Thr Gly Arg Gln Leu Val Ala Ala Val Gln Gln Lys 65 70 75 80 Phe Asp Arg Ile Asp Ile Leu Val Asn Ser Ala Gly Ile Thr Arg Asp 85 90 95 Lys Leu Leu Leu Ser Met Glu Ala Asp Asp Ile His Gln Val Ile Ala 100 105 110 Thr Asn Leu Val Gly Pro Met Phe Leu Thr Gln Ala Val Ala Leu Thr 115 120 125 Met Leu Arg Gln Arg Ser Gly Arg Ile Val Asn Ile Ser Ser Ala Ala 130 135 140 Ala Ser Arg Pro Gly Lys Gly Gln Ser Asn Tyr Ala Ala Ser Lys Ala 145 150 155 160 Gly Leu Glu Ala Phe Thr Arg Ala Met Ala Val Glu Leu Gly Ser Arg 165 170 175 Gly Ile Leu Val Asn Ala Val Ala Pro Gly Ile Val Lys Thr Gly Leu 180 185 190 Thr Glu Ala Leu Arg Glu Gly Ala Glu Pro Glu Leu Leu Ala Arg Gln 195 200 205 Val Ile Gly Ser Phe Ala Glu Pro Glu Ala Val Ala Glu Ala Val Ala 210 215 220 Tyr Leu Ala Ser Pro Arg Asn Thr His Thr Thr Gly Thr Val Leu Thr 225 230 235 240 Val Asp Gly Gly Leu Lys Met Val 245 31 382 PRT Streptomyces bikiniensis 31 Met Ser Ala Ser Leu Ser Pro Ala Arg Thr Arg Ala Ala Leu Arg Ala 1 5 10 15 Ser Ala Arg Ile Ser Thr Glu Leu Leu Leu Val Leu Leu Gly Thr Ala 20 25 30 Ala Val Ile Trp Leu Leu Gly Arg Met Trp Ser Ile Val Trp Pro Leu 35 40 45 Val Ile Gly Leu Leu Ile Thr Thr Leu Thr Trp Pro Phe Ala Arg Leu 50 55 60 Leu Arg Arg Leu Gly Trp Pro Pro Ala Leu Ala Ala Ser Val Val Thr 65 70 75 80 Val Leu Phe Leu Ala Val Thr Ala Gly Thr Val Ala Leu Ile Ala Val 85 90 95 Pro Val Ala Ser Gln Ser Gly Glu Leu Ala Asp Gly Val Val Glu Gly 100 105 110 Ile Gln Arg Leu Arg Glu Trp Thr Ala Gly Pro Pro Leu Asn Ile Gly 115 120 125 Asp Asp Gln Ile Thr Gly Ala Leu Asp Thr Ala Thr Asp Arg Leu Gln 130 135 140 Asn Ser Val Gly Ser Leu Leu Thr Thr Leu Ala Thr Gly Val Gly Thr 145 150 155 160 Val Val Asn Gly Val Val Thr Ala Val Leu Ala Leu Phe Leu Met Phe 165 170 175 Phe Phe Leu Lys Asp Gly Pro Arg Phe Leu Pro Trp Leu Ala Arg Gln 180 185 190 Leu Pro Gly Arg Leu Ala Thr Asp Ala Thr Thr Ile Ala Glu Arg Gly 195 200 205 Trp Asp Thr Leu Gly Ala Phe Val Arg Ser Gln Ala Ala Val Gly Leu 210 215 220 Leu Asp Ala Val Leu Ile Gly Ile Gly Leu Trp Ile Leu Gly Val Pro 225 230 235 240 Leu Val Leu Pro Leu Ala Val Leu Thr Phe Val Ser Ala Phe Val Pro 245 250 255 Ile Ile Gly Ala Leu Leu Ala Gly Phe Val Ala Val Leu Ile Ala Leu 260 265 270 Val Ser Asn Gly Leu Thr Asp Ala Leu Ile Val Leu Ala Ile Ile Val 275 280 285 Val Val Gln Gln Leu Glu Gly Asn Val Phe Gln Pro Met Ile Gln Ser 290 295 300 Arg Gly Leu Gly Leu His Ala Ala Val Val Leu Leu Ala Val Thr Leu 305 310 315 320 Gly Gly Ser Leu Ala Gly Ile Val Gly Ser Leu Leu Ala Val Pro Val 325 330 335 Ala Ala Leu Val Ala Val Val Trp Gly Tyr Val Arg Glu Gln Leu Ser 340 345 350 Asp Pro Pro Gln Leu Asp Ala Asp Gly Gly Thr Arg Pro Gly Pro Asp 355 360 365 Gly Ala Pro Glu Ser Val Val Pro Ala Glu Ile Pro Ala Ser 370 375 380 32 487 PRT Streptomyces bikiniensis 32 Met Thr Ala Thr Thr Arg Arg Asp Pro Ala Ala Val Pro Asp Gly Gly 1 5 10 15 Thr Ala Glu Pro Val Pro Ser Pro Ala Ala Pro Asp Gly Arg Ala Ala 20 25 30 Gln Thr Val Pro Ser Pro Ala Ala Pro Asp Ser Gly Ala Ala Glu Ser 35 40 45 Ala Pro Ser Thr Ala Ala Asp Gly Arg Ala Glu Gln Thr Val Cys Ser 50 55 60 Leu Ala Ala Asp Gly Thr Ala Asp Gly Arg Gly Arg Ala Pro Gly Ala 65 70 75 80 Ala Val Gly Val Gly Asp Ala Gly Pro Arg Arg Arg Trp Trp Arg Arg 85 90 95 Arg Gly Ala Ala Val Thr Gly Cys Ser Val Phe Leu Ala Ala Pro Asp 100 105 110 Gly Arg Ala Ala Gln Thr Val Pro Ser Pro Ala Ala Pro Asp Ser Gly 115 120 125 Ala Ala Glu Ser Ala Pro Ser Thr Ala Ala Asp Gly Arg Ala Glu Gln 130 135 140 Thr Val Cys Ser Leu Ala Ala Asp Gly Thr Ala Asp Gly Arg Gly Arg 145 150 155 160 Ala Pro Gly Ala Ala Val Gly Val Gly Asp Ala Gly Pro Arg Arg Arg 165 170 175 Trp Trp Arg Arg Arg Gly Ala Ala Val Thr Gly Cys Ser Val Phe Leu 180 185 190 Ala Val Ser Val Ala Gly His Gly Arg Leu Pro Gly Leu Pro Gly Arg 195 200 205 Leu Ser Ser Leu Ala Glu Thr Leu Leu Pro Trp Ser Ala Leu Ala Val 210 215 220 Pro Val Leu Val Thr Ala Ala Leu Leu Trp Arg Ala Arg Val Ala Ala 225 230 235 240 Val Val Ala Leu Val Val Pro Ala Val Ala Trp Leu Thr Ala Phe Gly 245 250 255 Gly Ala Leu Thr Asp Lys Thr Thr Pro Gly Gly Asp Leu Thr Leu Val 260 265 270 Ser His Asn Val Glu Gln Ala Asn Pro Asp Pro Ala Gly Thr Val Arg 275 280 285 Ser Leu Leu Ala Ala Gly Ala Asp Val Leu Ala Leu Glu Glu Leu Ser 290 295 300 Pro Ala Thr Ala Pro Ala Tyr Glu Arg Ala Leu Ala Glu Ser Tyr Pro 305 310 315 320 Tyr His Phe Tyr Glu Gly Thr Val Gly Leu Trp Ser Val His Pro Leu 325 330 335 Ser Asp Ala Arg Ala Val Pro Ile Met Pro Trp Thr Arg Ala Met Arg 340 345 350 Ala Thr Val Asp Ala Pro Gly Gly Pro Leu Ala Val Tyr Val Ala His 355 360 365 Leu Pro Ser Val Arg Val Gly Pro Gly Gly Phe Thr Ala Gly Ala Arg 370 375 380 Asp Glu Ala Leu Gly Leu Leu Ala Ala Glu Val Arg Ala Glu Pro Val 385 390 395 400 Arg Arg Val Val Leu Leu Gly Asp Leu Asn Gly Ser Thr Asp Asp Arg 405 410 415 Ala Leu Arg Pro Leu Thr Asp Arg Leu Val Ser Ala Gln Ala Ala Ala 420 425 430 Gly Ala Gly Phe Gly Phe Thr Trp Pro Ala Arg Leu Pro Val Val Arg 435 440 445 Ile Asp Gln Ile Leu Leu Gly Gly Val Arg Ala Ala Ser Ala Trp Thr 450 455 460 Leu Pro Ala Thr Ala Ser Asp His Leu Pro Val Ala Ala Arg Ile His 465 470 475 480 Leu Ala Pro Asp Pro Ala Pro 485 33 231 PRT Streptomyces bikiniensis 33 Met Thr Ala Tyr Val Ile Leu Glu Glu His Pro Leu Arg Pro Asp Glu 1 5 10 15 Asp Gly Pro Leu Ile Glu Val Asp Arg Thr Ala Ala His Glu Ala Gly 20 25 30 Val Gly Gly Glu Ser Thr Val Pro Val Arg Ser Gly Glu Arg His Ser 35 40 45 Gln Arg Arg Leu Leu Glu Leu Leu Leu Ile Pro Ser Gly Asn Asn Val 50 55 60 Ala Arg Leu Leu Ala Arg Trp Asp Ser Gly Ser Gln Ala Ala Phe Val 65 70 75 80 Thr Lys Met Arg Arg Ala Ala Val Arg Leu Gly Met Lys Asp Thr Val 85 90 95 Tyr Thr Gly Ala Ser Gly Ile Glu Pro Thr Thr Thr Ser Thr Ala Ala 100 105 110 Asp Gln Val Arg Leu Thr Arg Ala Ala Met Glu Asp Pro Val Phe Arg 115 120 125 Ala Val Val Ala Thr Arg Glu Thr Thr Val Pro Gly Leu Gly Thr Ile 130 135 140 Thr Asn Thr Asn Pro Leu Leu Asp Thr Pro Gly Val Leu Gly Val Lys 145 150 155 160 Thr Gly Ser Ser Thr Pro Ala Gly Gly Asn Leu Leu Trp Ala Tyr Glu 165 170 175 Val Arg Val Gly Gly Ala Pro Arg Leu Leu Val Gly Ala Val Leu His 180 185 190 Gln Arg Ala Asn Thr Thr Pro Ala Glu Gly Leu Arg Ala Ala Val Glu 195 200 205 Ala Ala Arg Gly Leu Leu Thr Ala Val Arg Glu Arg Leu Ala Ala Ala 210 215 220 Gly Thr Gln Gly Gly Glu Arg 225 230 34 386 PRT Streptomyces bikiniensis 34 Met Ala Leu Thr Val Gly Val Leu Val His Asp Ser Val Leu Arg Arg 1 5 10 15 Ser Leu His Glu Gly Ala Gly Arg Ala His Val Ala Leu Ala Thr Ala 20 25 30 Leu Glu Asp Ala Asp Ala Ala Gly Glu Glu Gly Pro Arg Val Ser Pro 35 40 45 Glu Glu Leu Pro Glu Ala Leu Leu Arg Gln Ile Glu His Gly Gly Glu 50 55 60 Ala Thr Leu Tyr Glu Asp Gly Pro Pro Ala Pro Val Phe Arg Ala Ala 65 70 75 80 Arg Arg Glu Gly Gly Lys Leu Tyr Ala Val Glu Val Asp Met Thr Ala 85 90 95 Asp Leu Leu Thr Arg Gln Ala Leu Asp Arg His Met Trp Lys Tyr Ser 100 105 110 Leu Leu Thr Leu Gly Val Val Val Pro Ala Thr Ala Leu Ala Thr Glu 115 120 125 Leu Pro Ala Arg Arg Leu Arg Arg Val Ala Arg Thr Ala Arg Arg Ile 130 135 140 Thr Ala Gly Asp Leu Asp Ala Arg Thr Gly Thr Val Arg Gly Gly Asp 145 150 155 160 Glu Val Ala Glu Ile Ser Ala Val Val Asp Ser Met Ala Asp Ser Leu 165 170 175 Gln Gln Arg Ile Asp Thr Glu Gln Arg Phe Thr Ala Asp Val Ala His 180 185 190 Glu Leu Arg Thr Pro Leu Met Gly Leu Val Thr Ser Ala Glu Leu Leu 195 200 205 Pro Glu Gly Glu Val Thr Asp Met Val Gln Ser Arg Val Arg Val Leu 210 215 220 Arg Asp Leu Val Glu Asp Leu Leu Glu Val Ser Arg Leu Asp Ala Gly 225 230 235 240 Ala Glu Thr Ala Gln Gln Gly Pro Val Asp Leu Gly Ala Leu Val Arg 245 250 255 Asp Ser Val Ala Arg Thr Gly Leu Ala Ala Gln Val Thr Arg Gln Gly 260 265 270 Ala Ala Val Val Glu Ser Asp Pro Arg Arg Leu Asp Arg Ile Val Ser 275 280 285 Asn Leu Val Val Asn Ala His Arg His Gly Ala Gly Arg Val Glu Val 290 295 300 Thr Val Ala Gly Arg Thr Val Thr Val Arg Asp His Gly Pro Gly Phe 305 310 315 320 Pro Ala Asp Leu Leu Ser His Gly Pro Gln Arg Phe Arg Thr Gly Ser 325 330 335 Ala Glu Arg Gly His Gly His Gly Leu Gly Leu Thr Ile Ala Ser Gly 340 345 350 Gln Ala Arg Val Ile Gly Ala Thr Leu Ala Phe Ala Asn Ala Arg Asp 355 360 365 Gly Gly Ala Val Ala Thr Leu Ser Leu Pro Glu Asp Gly Gln Thr Ser 370 375 380 Glu Ala 385 35 228 PRT Streptomyces bikiniensis 35 Val Thr Val Leu Leu Val Glu Asp Asp Glu Val Ile Arg Arg Ser Val 1 5 10 15 Ala Met Ser Leu Glu Arg Tyr Gly Tyr Arg Val Arg Val Ala Ala Asp 20 25 30 Gly Leu Thr Gly Leu Glu Leu Phe Arg Glu Gly Arg His Asp Leu Val 35 40 45 Leu Leu Asp Val Met Leu Pro Gly Leu Asp Gly Ile Gly Leu Cys Arg 50 55 60 Arg Ile Arg Glu Thr Ala Thr Asp Pro Ile Leu Met Met Ser Ala Arg 65 70 75 80 Gly Asp Ala Leu Asp Val Val Ser Gly Leu Glu Ala Gly Ala Asp Asp 85 90 95 Tyr Val Val Lys Pro Val Asp Thr Ala Val Leu Val Ala Arg Ile Arg 100 105 110 Ser Leu Leu Arg Arg Ala Ala Phe Val Ser Pro Ala Pro Gly Pro Ala 115 120 125 Asp Pro Ala Thr Pro Ala Gly Pro Leu Leu Phe Gly Asp Leu Ser Leu 130 135 140 Asp Pro Ala Ala Leu Glu Val Arg Arg Gly Gly Glu Arg Ile Ala Leu 145 150 155 160 Ala Pro Thr Glu Leu Arg Leu Leu Leu Gln Phe Ala Ala His Pro Gly 165 170 175 Ile Val Leu Asp Arg Gln Thr Leu Leu Arg Glu Val Trp Asp Tyr Gly 180 185 190 Trp Asp Gly Asp Thr Arg Val Val Asp Leu Cys Val Gln Arg Leu Arg 195 200 205 Lys Lys Ile Gly Ala Glu Arg Val Glu Thr Val Arg Gly Phe Gly Tyr 210 215 220 Lys Trp Lys Arg 225 36 476 PRT Streptomyces bikiniensis 36 Met Pro Glu Ser Arg Pro Ala Pro Glu Pro Thr Lys Thr Glu Asp Gly 1 5 10 15 Thr Asp Ala Arg Pro Asp Thr Pro Ala Arg Pro Gly Asp Thr His Pro 20 25 30 Val Asp Gln Met Leu Pro Pro Leu Lys Leu Phe Ser Ala Gly Leu Gln 35 40 45 His Val Ala Ala Met Tyr Ala Gly Val Val Ala Pro Pro Leu Val Val 50 55 60 Gly Ile Gly Val Gly Leu Ser Thr Ala Asp Ile Ala Phe Leu Met Ser 65 70 75 80 Ala Ser Leu Phe Thr Ser Gly Ile Ala Thr Leu Leu Gln Thr Leu Gly 85 90 95 Phe Trp Lys Val Gly Ala Arg Leu Pro Phe Val Asn Gly Val Ser Phe 100 105 110 Ala Gly Val Ala Pro Met Leu Ala Ile Ala Lys Ala Glu Gly Pro Asp 115 120 125 Asp Ala Leu Pro Val Ile Tyr Gly Ala Val Ile Val Ala Gly Val Phe 130 135 140 Gly Phe Leu Leu Ala Pro Phe Phe Cys Lys Leu Ile Arg Phe Phe Pro 145 150 155 160 Pro Val Val Thr Gly Thr Val Ile Thr Leu Ile Gly Val Ser Leu Leu 165 170 175 Pro Val Ala Phe Asn Trp Ala Gln Gly Gly Asn Ala Gln Ala Pro Asp 180 185 190 Tyr Gly Ser Leu Thr Tyr Ile Gly Leu Ala Thr Ala Thr Leu Leu Ile 195 200 205 Thr Val Val Leu Arg Arg Val Leu Thr Gly Phe Leu Lys Gln Ile Ser 210 215 220 Ile Leu Leu Gly Leu Val Ala Gly Thr Leu Leu Ser Leu Pro Leu Gly 225 230 235 240 Val Ala Asp Phe Ser Ala Val Gly Asp Ala Asp Val Ile Gly Leu Pro 245 250 255 Thr Pro Phe His Phe Gly Ala Pro Gln Phe Ala Ala Ala Ala Ile Ile 260 265 270 Ser Met Cys Ile Val Met Leu Val Ser Met Thr Glu Ser Thr Ala Asp 275 280 285 Val Leu Ala Leu Gly Glu Ile Val Glu Arg Pro Ala Asp Glu Lys Thr 290 295 300 Leu Ala Ala Ala Leu Arg Ala Asp Gly Leu Gly Thr Ala Leu Ser Pro 305 310 315 320 Leu Phe Asn Gly Phe Ala Ala Ser Ala Phe Ala Gln Asn Val Gly Leu 325 330 335 Val Ala Ile Thr Lys Val Arg Ser Arg Phe Val Val Ala Ala Ala Gly 340 345 350 Gly Ile Leu Leu Leu Leu Gly Leu Cys Pro Leu Leu Ala Ser Val Val 355 360 365 Ala Leu Ile Pro Gln Pro Val Leu Gly Gly Val Gly Ile Ala Leu Phe 370 375 380 Gly Thr Val Ala Ala Ser Gly Ile Gln Thr Leu Ala Gly Ala Ala Leu 385 390 395 400 Glu Arg Gly Asp Asn Val Leu Ile Val Ala Ile Ser Leu Gly Ala Gly 405 410 415 Ile Ile Pro Ile Ala Ala Pro Asp Phe Tyr His Ala Phe Pro Glu Gly 420 425 430 Ala Arg Ile Val Leu Asp Ser Gly Ile Ser Thr Gly Cys Val Val Ala 435 440 445 Val Leu Leu Asn Leu Ala Phe Asn His Leu Gly Arg Arg Thr Asp Pro 450 455 460 Ala Pro Glu Thr Leu Pro Ala Pro Ala Ala His His 465 470 475 37 238 PRT Streptomyces bikiniensis 37 Met Pro Pro Ala Asp Asp Pro Tyr Ala Leu Pro Arg Phe Asp Pro Thr 1 5 10 15 Arg Ala Ala Ala Val Arg Ala Gln Leu Gly Leu Thr Leu Gly Gln Val 20 25 30 Ala Trp Ala Val Thr Ala Tyr Cys Gly His Pro Ala His Pro Gly Leu 35 40 45 Val Glu Ala Trp Glu Ala Gly Thr Ala Thr Pro Asp Asn Thr Gln Val 50 55 60 Lys Ala Leu Ala Ala Ala Leu Trp Cys Ser Pro Val Asp Leu Val Glu 65 70 75 80 Glu Pro Gly Thr Leu Ala Gln Cys Arg Thr Val Ala Gly Leu Thr Val 85 90 95 Asn Glu Thr Ala Thr Glu Leu Gly Leu Thr Arg Gly Gln Trp Glu Asp 100 105 110 Ala Glu Arg Arg Asn Arg Trp Gln Gly Thr Pro Ala Gln Thr Asp Ala 115 120 125 Leu Leu Arg Val Leu Cys Pro Pro Pro Ala Cys Phe Val Ala Ala Cys 130 135 140 Gly Arg Thr Gly Arg Leu Arg Val Leu Leu Arg Glu Ala Ala Thr Thr 145 150 155 160 Trp Trp Pro Pro Tyr Val Gly Ala Leu Ser Arg Ile Val Pro Leu Asp 165 170 175 Pro Ala Val Leu Gly His Ala Leu Glu Arg Leu His Leu Thr Tyr Gln 180 185 190 Gln Trp Glu Gly Ala Ala Gly Gly Pro Pro Arg Gln Ala Ala Arg Ala 195 200 205 Glu Ala Arg Ala Ala Asp Phe Leu Glu His Ile Asp Leu His Leu Trp 210 215 220 His His Val Arg Glu Val Leu Asn Pro Ala Arg Pro Ala Ser 225 230 235 38 612 PRT Streptomyces bikiniensis 38 Val Ser Gln Gly Pro Ala Leu Leu Pro Arg Ala Thr Asp His Ala Ser 1 5 10 15 Pro Thr Pro Pro His Pro Val Asp Glu Ile Leu Pro Ala Arg Arg Met 20 25 30 Leu Pro Ala Ala Leu Gln His Val Ala Ser Met Tyr Ala Gly Leu Thr 35 40 45 Ala Pro Pro Leu Ile Ile Ser Ser Ala Leu Gly Leu Thr Pro Ala Gln 50 55 60 Leu Ser Ala Leu Leu Ala Ala Ala Leu Leu Ile Ala Gly Leu Gly Thr 65 70 75 80 Ile Ala Gln Thr Leu Gly Val Tyr Gly Val Gly Ala Gly Leu Pro Leu 85 90 95 Val Asn Gly Val Ser Phe Ala Val Val Ser Pro Ala Leu Ala Thr Ala 100 105 110 Ala Thr Gln Gly Arg Asp Gly Ala Leu Pro Ala Ile Phe Gly Ala Thr 115 120 125 Leu Val Ala Gly Leu Leu Cys Leu Leu Leu Ala Pro Val Phe Cys Arg 130 135 140 Leu Val Arg Phe Phe Pro Pro Val Val Ser Gly Cys Val Ile Thr Leu 145 150 155 160 Val Gly Ile Ser Leu Leu Pro Val Ala Gly Thr Trp Ala Arg Gly Gly 165 170 175 Asp Ala Glu Ala Ala Gly Phe Gly Ser Pro Ala Asp Leu Ala Leu Ala 180 185 190 Ala Thr Thr Leu Val Ile Thr Leu Thr Val His Arg Met Leu Ser Gly 195 200 205 Arg Phe Leu Gly Arg Val Ala Ile Leu Ile Gly Met Leu Ala Gly Thr 210 215 220 Leu Ile Ala Ile Pro Leu Gly Lys Val Asp Leu Asp Pro Leu Ala Gln 225 230 235 240 Ala Pro Leu Phe Ala Leu Pro Thr Pro Phe Gly Phe Gly Thr Pro Gln 245 250 255 Phe Val Pro Thr Val Ile Ala Thr Ala Ala Val Val Met Ile Val Ser 260 265 270 Met Met Glu Ser Thr Ala Ala Leu Leu Ala Leu Gly Ala Val Ala Glu 275 280 285 Arg Pro Val Arg Asp Arg Thr Ile Ala Gly Ser Leu Arg Ala Leu Gly 290 295 300 Leu Ala Thr Val Leu Gly Gly Val Leu Gly Ser Phe Thr Ser Thr Ser 305 310 315 320 Tyr Ala Gln Asn Val Gly Leu Val Ser Leu Ser Arg Ile Arg Ser Arg 325 330 335 Tyr Val Val Thr Leu Cys Gly Ala Val Leu Val Leu Met Gly Phe Val 340 345 350 Pro Val Leu Gly Ser Phe Val Ala Leu Val Pro Leu Pro Val Leu Gly 355 360 365 Gly Ala Gly Val Val Phe Phe Gly Ser Val Ala Val Thr Gly Ile Arg 370 375 380 Thr Leu Ala Lys Ala Ala Leu Gly Thr Gly His Asn Ala Val Ile Val 385 390 395 400 Ser Val Thr Leu Ala Phe Gly Leu Phe Pro Val Leu Asp Pro Asp Phe 405 410 415 Tyr Ala Arg Leu Pro Ala Pro Val Ala Thr Val Leu Gly Ser Gly Ile 420 425 430 Thr Ala Gly Cys Leu Val Ala Val Leu Leu Asn Tyr Leu Leu Asn His 435 440 445 Leu Gly Arg Gly Thr Glu Ala Asp Pro Asp Ala Ile Ser Ala Glu Gln 450 455 460 Val Thr Ala Leu Asp Thr Ala Asp Thr Val Leu Gly Pro Lys Arg Ser 465 470 475 480 Ser Asp Trp Thr Pro Phe Gln Pro Ser Gly Ser Pro Ser Gly Thr Pro 485 490 495 Asp His Gly Arg His Thr Arg Gly Thr Ala Arg Pro Ala Pro Ala Trp 500 505 510 Pro Tyr Val Thr Gly Pro Val Asp Pro Thr Asp Thr Gly Arg His His 515 520 525 Arg Pro His Glu Val Pro Ala Pro Pro His Arg Pro Asp Glu Val Pro 530 535 540 Pro Pro Leu His Pro Ser Ala Ala His Glu Gly Glu Pro Pro Pro Ala 545 550 555 560 Val Thr Glu Asn Ala Val Phe Pro Gly Pro Leu His Pro Leu His Pro 565 570 575 Leu His Pro Arg Pro Thr Gly Arg Pro Asp Arg Pro Arg Gln Arg His 580 585 590 Ser Ala Glu Ala Asp Pro Trp Gln His Pro Gln Thr Pro Ser Ala Ser 595 600 605 Gly Asp Ser Gln 610 39 223 PRT Streptomyces bikiniensis 39 Met Thr Thr Val Ser Ala Ala Arg His Arg Ala Gly Gly Ser Pro Arg 1 5 10 15 Gly Gly Thr Ser Arg Pro Gly Pro Asp Glu Arg Ile Ala Gln Val Val 20 25 30 Ala Glu Ala Leu Gly Ser Ala Arg Thr Val Leu Asp Pro Asp Ala Leu 35 40 45 Pro Gly Leu Gly Thr Thr Arg Leu Pro Phe Gly Asp Gly Arg Phe Asp 50 55 60 Ala Ala Met Met Leu Cys Asn Ala Pro Gly Val Pro Asp Ala Leu Ser 65 70 75 80 Arg Leu Gly Glu Leu Arg Arg Val Thr Arg Gly Pro Val Val Val Leu 85 90 95 Ala Thr Asp Pro Ser Arg Val Arg Ser Phe Trp Leu Asp Arg Tyr Ala 100 105 110 Pro Glu Val Leu Ala Val Glu Ala Arg Arg His Pro Pro Ile Ala Asp 115 120 125 Leu Thr Ala Val Leu Gly Gly Ser Ala Glu Val Arg Ser Val Pro Val 130 135 140 Pro Leu Asp Cys Thr Asp Thr Phe Asp Glu Ala Tyr Tyr Gly Arg Pro 145 150 155 160 Glu Lys Leu Leu Asp Pro Ser Ala Arg Gln Ala Gly Ser Ala Trp Ser 165 170 175 Phe Val Asp Asp Arg Val Arg Glu Glu Phe Asp Thr Thr Leu Arg Arg 180 185 190 Glu Leu Arg Ser Gly Glu Trp Asp Glu Arg Phe Gly His Leu Arg Arg 195 200 205 Arg Pro Val Tyr Glu Gly Ser Leu Val Ile Val Arg Ala Val Pro 210 215 220 40 251 PRT Streptomyces bikiniensis 40 Met Thr Thr Gly Thr Asp Ser Thr Thr Trp Phe Arg Arg Tyr Ser Ser 1 5 10 15 Thr Pro Ala Pro Arg Arg Arg Leu Ala Val Leu Pro His Ala Gly Gly 20 25 30 Ser Ala Ser Phe Phe His Ala Trp Gly Ser Ala Phe Gly Gly Asp Thr 35 40 45 Glu Val Leu Val Ala Gln Tyr Pro Gly Arg Gln Glu Arg Phe Asn Glu 50 55 60 Pro Phe Val Asp Arg Met Asp Val Leu Ala Asp Arg Val Thr Ala Ala 65 70 75 80 Leu Leu Pro Leu Ala Asp Val Pro Leu Thr Leu Phe Gly His Ser Met 85 90 95 Gly Ala Ser Leu Ala Tyr Glu Val Ala Leu Arg Leu Glu Glu Arg His 100 105 110 Arg Val Thr Pro Ala Ala Leu His Val Ser Ser Arg Lys Ala Pro His 115 120 125 Arg Leu Thr Pro Leu Asp Leu His Arg Lys Gly Asp Asp Glu Leu Val 130 135 140 Ala Val Leu Arg Gly Leu Gly Gly Thr Asp Thr Ala Leu Leu Asp Asp 145 150 155 160 Pro Asp Ile Arg Gln Leu Val Leu Pro Ala Val Arg Ala Asp Phe Thr 165 170 175 Val Val Ser Thr Tyr Gly Pro Arg Val Pro Thr Ala Val Gly Cys Pro 180 185 190 Val His Ala Trp Ile Gly Asp Thr Asp Pro Asn Val Ala Val Gly Asp 195 200 205 Met Asp Ala Trp Ala Asp Val Ala Pro Glu Gly Phe Arg Val Arg Val 210 215 220 Leu Pro Gly Gly His Phe Tyr Leu Leu Gln Gln His Glu Thr Leu Met 225 230 235 240 Arg Glu Leu Ser Gly His Leu Ala Gly Asp Arg 245 250 41 316 PRT Streptomyces bikiniensis 41 Met Asp His Arg Arg Ala Arg Ala Ala Leu Pro Leu Ser Arg His Val 1 5 10 15 Arg Asp Gly Asp Ala Pro Ser Gly Thr Ala Ala Leu Ala Gly Asp Thr 20 25 30 Gly Arg Arg Ala Ala Pro Arg Cys Thr Asp Pro Pro Glu Arg Ala Ala 35 40 45 Arg Val Gly Gln Gly Pro Gly Asp Arg Gly Ala Arg Arg Arg Val Pro 50 55 60 Arg Ala Ala Asp Arg Pro Leu Ala Ala Pro Pro Ala Arg Leu Ala Pro 65 70 75 80 Gly Pro Leu Ser Ala Gly Arg Pro Gln Pro Gly Gln His Pro Gly Thr 85 90 95 Gly Gly Val His Ala Arg Ala Gly Gly Arg Gly Ala Pro Val Arg Leu 100 105 110 His Ala Gly Gly Ala Gly Ala Gly Ala Gly Arg Val Glu Gly Thr Pro 115 120 125 Ala Ala Gly Pro His Arg Glu Pro Gly Val Val Arg Arg Pro Arg Gly 130 135 140 Leu Ala Val His Arg Gly Arg Pro Arg Asp Arg Arg Ala Gly Ala Asp 145 150 155 160 Arg Gly Pro Arg Arg Gly Ala Pro His Gly Ala Asp Ala Gly Arg Gly 165 170 175 Val Arg Pro Asp Thr Gly Leu Pro Gln Val Ala Ala Pro Ala Ala Arg 180 185 190 Gly Ala Asp Arg Ala Ala Asp Arg Leu Val His Ala Gly Pro Ala Gly 195 200 205 Arg Ala Gln Arg Arg Arg Gly Gly Gly His Pro Gly Gly Ala Ala Pro 210 215 220 Pro Gly Pro Asp Gly Glu Arg Leu Gly Arg Leu Leu Pro Arg Pro Gly 225 230 235 240 Pro Ala Val Arg Arg Gln Gln Pro Glu Ala Gly Ile Gly Arg Trp Ser 245 250 255 Gly Arg Arg Gly Arg Arg Phe Gly Arg His Gly Arg Arg His Arg Asp 260 265 270 Arg Arg Gly Thr Ala Glu Leu Gly His His Arg Pro Glu Val Gly Ser 275 280 285 Gly Thr Val Gln Asp Arg Asp Val His Gly Pro Arg Glu Asp Arg Val 290 295 300 Arg Asp His Gly His Arg Cys Arg Glu Leu Pro Gly 305 310 315 42 240 PRT Streptomyces bikiniensis 42 Met Phe Arg Thr Glu Glu Lys Arg Pro Val Ala Thr Gly Thr Thr Ala 1 5 10 15 His Asp Ala Val Arg Gly His Pro Asp Ala His Ala Ala Gly Phe Gly 20 25 30 Arg Pro Arg Arg Val Thr Val Ala Val Tyr Ala Ala Asp Pro Val Leu 35 40 45 Arg Val Gly Val Val Gln Gln Leu Arg Gln Arg Pro Glu Thr Glu Leu 50 55 60 Val Asp Asp Ala Asp Ala Glu Asn Ala Gln Val Ser Leu Val Val Val 65 70 75 80 Asp Ala Leu Asp Asp Asp Val Thr Ala Leu Leu Thr Arg Leu Ser Tyr 85 90 95 Asn Gly Ala Thr Arg Ala Gly Leu Val Ile Gly Thr Leu Gly Val Gly 100 105 110 Ala Leu Gln Arg Val Val Glu Cys Gly Val Ser Ala Val Leu Arg Arg 115 120 125 Ala Glu Ala Asp Gln Asp Gln Leu Val Gln Leu Val Leu Ala Val Ala 130 135 140 Asn Gly Glu Gly Val Leu Pro Gly Asp Leu Leu Gly Glu Leu Leu Gly 145 150 155 160 His Val Gly Ser Leu Arg Arg Ala Ala Leu Asp Pro Gly Ala Leu Pro 165 170 175 Leu Ser Thr Leu Thr Ser Arg Glu Ala Glu Met Leu Arg Leu Val Ser 180 185 190 Glu Gly Leu Asp Thr Ala Ala Ile Ala Arg Lys Thr Ser Tyr Ser Glu 195 200 205 Arg Thr Val Lys Asn Val Leu His Glu Ile Thr Thr Arg Leu Gln Leu 210 215 220 Arg Asn Arg Ala His Ala Val Gly Tyr Ala Leu Arg Asn Gly Leu Ile 225 230 235 240 43 1066 PRT Streptomyces bikiniensis 43 Met Lys Thr Ala Gly Pro Gly Gly Arg His Arg Arg Gly Arg Leu Ala 1 5 10 15 Ser Ala Leu Leu Leu Leu Val Pro Leu Leu Gly Ala Thr Gly Val Ala 20 25 30 Gly Pro Asp Asp Pro Arg Thr Ala Ala Ala Ala Ala Asp Ala Ala Glu 35 40 45 Thr Thr Arg Ile Ala Tyr Ala Gly Thr Gly His Arg Ser Leu Gly Glu 50 55 60 Pro Ala Ser Thr Asp Ser Ser Thr Pro Leu Phe Gly Ala Gly Pro Thr 65 70 75 80 His Tyr Asp Thr Asp Pro Ser Ala Leu Gly Asp Arg Leu Val Phe Ala 85 90 95 Ser Arg Arg Asp Glu Lys His Pro Gln Ile Tyr Leu Arg Gly Ala Asp 100 105 110 Gly Gly Val Leu Arg Leu Thr Ser Gly Leu Asp Ala Ala Arg Pro Arg 115 120 125 Leu Thr Pro Asp Gly Gly Ser Val Leu Phe Asp Ala Ala Asp Pro Ala 130 135 140 Gly Gly Ser Gln Arg Asp Leu Trp Leu Val Arg Thr Asp Gly Thr Gly 145 150 155 160 Leu Thr Arg Leu Thr Asp Thr Pro Ala Ser Glu Glu Asp Pro Ala Val 165 170 175 Ser Pro Asp Gly Ala Arg Ile Ala Tyr Ser Ser Asp Ala Asp Pro Leu 180 185 190 Ala Gly Arg Gln Ile Tyr Val Arg Ala Leu Thr Gly Gly Ile Pro Thr 195 200 205 Arg Leu Thr Asp Pro Ala Arg Gly Thr Ala Ser Glu Pro Ala Trp Asn 210 215 220 Pro Val Asp Asp Asp Val Asn Arg Ala Trp Ile Ala Tyr Thr Ser Thr 225 230 235 240 Thr Thr Glu Asp Gly Arg Thr Arg Gln Arg Leu Arg Ile Thr Asp Gly 245 250 255 Thr Thr Asp Glu Thr Leu Phe Thr Gly Ala Tyr Ala Asn Trp Gln Gly 260 265 270 His Gly Ala Ala Trp Leu Pro Asp Gly Asp Gly Ile Val Phe Leu Ser 275 280 285 Pro Glu Thr Thr Cys Thr Cys Arg Thr Pro Tyr Asp His Val Phe Arg 290 295 300 Ser Val Val His Ala Asp Arg Glu Pro Ser Leu Val Leu Asp Glu Asp 305 310 315 320 Arg Asp Val Leu Ser Pro Thr Trp Ile Gly Thr Ala Glu Gly Gly His 325 330 335 Ala Ile Val Glu Arg Ser Ser Ala Ala Thr Ala His Thr Ala Thr Leu 340 345 350 Gln Asp Ile Arg Ala Asp Gly Ser Asp Pro Arg Asp Leu Gln Arg Lys 355 360 365 Ile Leu Arg Glu Asp Pro Gln Ala Asp Thr Asn Thr Asp Pro Ala Lys 370 375 380 Asp Pro Leu Phe Gln Pro Ala Pro Pro Phe Asp Pro Trp Thr Glu Arg 385 390 395 400 Gln Asn Tyr Thr Pro Asp Gly Arg Arg Leu Val Leu Thr Arg Phe Glu 405 410 415 Gly Pro Asp Asp Ala Arg Ile Glu Arg Ile Trp Thr Ala Asp Ala Asp 420 425 430 Gly Thr Asn Glu Ala Pro Met Pro Leu Asp Gly Arg Gly Ala Arg Asp 435 440 445 Trp Asp Thr Asp Pro Thr Phe Ser Pro Asp Gly Thr Arg Leu Ala Phe 450 455 460 Thr Arg Thr Ser Pro Gly Gly Val Gly Glu Ala Ala Gly Asp Ser Arg 465 470 475 480 Ile Leu Leu Ala Glu Val Ala Thr Gly Arg Ile Thr Gly Glu Ile Val 485 490 495 Pro Pro Ala Gly Glu Leu Arg Gly Gly Asp Ala Gln Pro Thr Trp Ser 500 505 510 Ser Asp Gly Thr Thr Leu Ala Phe Thr Arg Ala Arg Gln Ile Ala Gly 515 520 525 Gly Gly Gly Ser Lys His Val Trp Thr Ala Ser Thr Ala Asp Leu Thr 530 535 540 Arg Gln Arg Asp Leu Ser Ala Thr His Cys Pro Arg Asp Cys Asp Val 545 550 555 560 Ile Asp Asp Ser Pro Ala Phe Ser Pro Asp Gly Arg Ser Leu Ala Phe 565 570 575 Asn Arg Lys Asn Gly Gly Gly Arg Ile Asp Glu Arg Asn Gly Leu Leu 580 585 590 Leu Thr Thr Leu Ser Gly Asp Ala Cys Gln Val Leu Leu Pro Thr Ala 595 600 605 Ala Arg Gly Gln Asp Gly Ala Cys Glu Arg Glu Leu Pro Asp Thr Thr 610 615 620 Leu Thr Gly Pro His Gln Pro Arg Asp Ala Ala Trp Thr Ala Asp Gly 625 630 635 640 Lys Arg Leu Val Phe Ser Ser Arg Ala Ala Ala Ala Val Asn Ser Pro 645 650 655 Glu Lys Leu Asn Val Leu Asp Val Gly Ser Gly Asp Ile Thr Pro Leu 660 665 670 Thr Ala Glu Leu Ala Gly Arg Gln Lys Glu Pro Thr Val Gln Gln Ser 675 680 685 Val Asp Leu Ala Val Glu Ala Pro Ala Thr Thr Pro Asp Val Thr Val 690 695 700 Gly Ala Ser Gly Thr Val Thr Val His Val Val Asn His Gly Pro Ala 705 710 715 720 Ala Ser Pro Gly Thr Arg Leu Thr Val Val Pro Pro Ser Gly Val Arg 725 730 735 Ile Thr Gly Ile Glu Trp Pro Gly Gly Thr Cys Asp Ala Ala Ser Leu 740 745 750 Gln Cys Asp Leu Gly Val Val Glu Ala Gly Ala Gln Val Pro Val Asp 755 760 765 Val Thr Leu Thr Gly Val Thr Ala Gly Asp Ala Pro Val Asp Trp Ser 770 775 780 Val Thr Gly Ala Val Leu Asp Pro Arg Pro Gly Asp Asn Asp Gly Arg 785 790 795 800 Ser Val Ile Pro Val Arg Glu Ala Pro Pro Thr Pro Thr Pro Thr Pro 805 810 815 Thr Pro Thr Pro Thr Pro Thr Pro Thr Pro Thr Pro Thr Pro Thr Pro 820 825 830 Thr Arg Thr Pro Thr Pro Thr Pro Thr Pro Thr Arg Pro Pro Gln Pro 835 840 845 Pro Ala Pro Lys Ala Gly Pro Gly Val Arg Ile Thr Val Gln Pro Glu 850 855 860 Pro Gly Tyr Val Gly Gly Arg Val Val Val Thr Tyr Ser Val Arg Asn 865 870 875 880 Gly Arg Asn Ala Leu Ala Thr Gly Leu Arg Leu Arg Ile Gly Leu Pro 885 890 895 Ala Gly Val Pro His Gly Gly Leu Pro Ala Gly Cys Asp Arg Asn Gly 900 905 910 Ala Cys Ala Leu Pro Asp Leu Thr Pro Gly Thr Thr Ala Val Leu Arg 915 920 925 Val Val Leu Ser Pro Lys Lys Ala Met Thr Ala Arg Val Thr Ala Val 930 935 940 Leu Asp Thr Thr Gly Thr Asp Ala Asp Arg Ser Asp Asn Thr Ala Arg 945 950 955 960 Glu Arg Leu Arg Val Leu Gln Pro Arg Ile Val Ala Val Pro Asp Ile 965 970 975 Gly Lys Pro Gly Phe Val Thr Ser Val Arg Gly Val Asp Phe Pro Pro 980 985 990 Gly Val Pro Val Arg Phe Ser Trp Asn Pro Gly Ile Thr Ala Ala Ala 995 1000 1005 Ser Pro Thr Phe Pro Glu Ala Asp Gly Thr Phe Ile Gly Gln Leu Leu 1010 1015 1020 Ile Leu Ala Lys Asp Gln Thr Gly Pro Arg Thr Ile Thr Ala Ser Gly 1025 1030 1035 1040 Pro Gly Phe Ser Pro Val Lys Thr Asp Phe Leu Val Val Ser Gly Thr 1045 1050 1055 Val Gln Pro Pro Asp Gly Val Thr Arg Arg 1060 1065 44 22 PRT Artificial Sequence Synthetic Construct 44 Thr Thr Cys Gly Ala Tyr Ser Cys Ser Gly Val Ser Thr Thr Cys Thr 1 5 10 15 Thr Cys Gly Ser Ala Thr 20 45 23 PRT Artificial Sequence Synthetic Construct 45 Gly Cys Ser Ala Thr Gly Gly Ala Tyr Cys Cys Ser Cys Ala Arg Cys 1 5 10 15 Ala Arg Cys Gly Ser Val Thr 20 46 22 PRT Artificial Sequence Synthetic Construct 46 Ser Ser Cys Thr Ser Gly Thr Ser Gly Cys Ser Met Thr Ser Cys Ala 1 5 10 15 Tyr Cys Trp Ser Gly Cys 20 47 23 PRT Artificial Sequence Synthetic Construct 47 Gly Thr Ser Cys Cys Ser Gly Thr Ser Cys Cys Arg Thr Gly Ser Ser 1 5 10 15 Cys Tyr Thr Cys Ser Ala Cys 20 48 22 PRT Artificial Sequence Synthetic Construct 48 Ala Ser Arg Thr Gly Ser Gly Cys Arg Thr Thr Ser Gly Thr Ser Cys 1 5 10 15 Cys Ser Ser Trp Ser Ala 20 49 21 DNA Artificial Sequence Synthetic Construct 49 cgtcagcctg atcctcgccg a 21 50 21 DNA Artificial Sequence Synthetic Construct 50 tccaggtggc cgacgttcgt c 21 51 21 DNA Artificial Sequence Synthetic Construct 51 aacgagatcc cgccgggcct c 21 52 17 DNA Artificial Sequence Synthetic Construct 52 cgcgttgctg ggcgagg 17 53 21 DNA Artificial Sequence Synthetic Construct 53 ggacgtctgc cggagggttc c 21 54 21 DNA Artificial Sequence Synthetic Construct 54 ggcccgttgg gcacggacag a 21 55 30 DNA Artificial Sequence Synthetic Construct 55 tttgcatgcg atgttgacga tctcctcgtc 30 56 30 DNA Artificial Sequence Synthetic Construct 56 ggaagcttca tatgttctct ccggaatgtg 30 57 31 DNA Artificial Sequence Synthetic Construct 57 ttaagctttc tagagaggag aggccgtgaa c 31 58 31 DNA Artificial Sequence Synthetic Construct 58 aaagaattcg aactcgagca cggactcgtt g 31 59 21 DNA Artificial Sequence Synthetic Construct 59 gacacggccg gtgagagcag c 21 60 23 DNA Artificial Sequence Synthetic Construct 60 cttctagatg tcgcggtgta cgg 23 61 42 DNA Artificial Sequence Synthetic Construct 61 cttaagggtt aattaaggag gacacatatg tccggagaat tc 42 62 5 PRT Artificial Sequence Synthetic Construct 62 Met Ser Gly Glu Phe 1 5 

What is claimed is:
 1. A recombinant DNA molecule that encodes a polypeptide, module or domain derived from a chalcomycin polyketide synthase (PKS) gene cluster.
 2. The recombinant DNA molecule of claim 1 that comprises a sequence encoding a chalcomycin polyketide synthase module selected from the group consisting of modules 0 to
 7. 3. The recombinant DNA molecule of claim 2 that comprises a sequence encoding a chalcomycin polyketide synthase polypeptide selected from the group consisting of ChmGI, ChmGII, ChmGIII, ChmGIV, and ChmV.
 4. The recombinant DNA molecule of claim 1 that comprises a coding sequence for a chalcomycin modifying enzyme.
 5. The recombinant DNA molecule of claim 4 that comprises a coding sequence for a chalcomycin P450 hydrolase enzyme selected from the group consisting of ChmHI, ChmPI, and ChmPII.
 6. A vector that comprises a DNA molecule of claim
 1. 7. The vector of claim 6 that is an expression vector.
 8. A recombinant host cell comprising the vector of claim 6
 9. A recombinant host cell comprising a DNA molecule of claim 1 integrated into the cell chromosomal DNA.
 10. A chimeric PKS that comprises at least one domain of a chalcomycin PKS.
 11. A cell comprising the chimeric PKS of claim 10
 12. A modified functional chalcomycin PKS that differs from the S. bikiniensis chalcomycin PKS by the inactivation of at least one domain of the chalcomycin PKS and/or addition of at least one domain of a non-chalcomycin PKS.
 13. The modified functional chalcomycin PKS of claim 12, wherein the domain of the chalcomycin PKS or the non-chalcomycin PKS is selected from the group consisting of a loading domain, a thioesterase domain, an AT domain, a KS domain, an ACP domain, a KR domain, a DH domain, and an ER domain.
 14. A cell comprising the PKS of claim 12
 15. A method to prepare an chalcomycin derivative which method comprises providing extender units to the cell of claim
 14. 16. A recombinant expression system capable of producing a chalcomycin synthase domain in a host cell, said system comprising an encoding sequence for a chalcomycin polyketide synthase domain, and said encoding sequence being operably linked to control sequences effective in said cell to produce RNA that is translated into said domain.
 17. A host cell modified to contain a recombinant expression system of claim
 16. 18. An isolated polypeptide encoded by a recombinant polynucleotide of claim
 1. 19. A recombinant host cell comprising a S. bikiniensis chalcomycin PKS polypeptide selected from the group consisting of ChmGI, ChmGII, ChmGIII, ChmGIV, and ChmV.
 20. The host cell of claim 19 that is S. fradiae.
 21. A recombinant S. bikiniensis cell in which a chmGI, chmGII, chmGIII, chmGIV, or chmV is disrupted so as to reduce or eliminate production of chalcomycin.
 22. A recombinant DNA molecule encoding a first protein comprising one or more modules of a chalcomycin PKS and a second protein comprising one or more modules of a tylosin PKS or spiramycin PKS.
 23. The DNA molecule of claim 22 wherein the hybrid polyketide synthase comprises one or more polypeptides of a chalcomycin PKS and one or more polypeptides of a tylosin PKS or spiramycin PKS.
 24. A recombinant host cell comprising a hybrid polyketide synthase comprising one or more modules of a chalcomycin PKS and one or more modules of a tylosin PKS or spiramycin PKS.
 25. A recombinant DNA molecule, comprising a sequence of at least about 200, optionally at least about 500, basepairs with a sequence identical or substantially identical to a protein encoding region of SEQ ID NO:1.
 26. The DNA molecule of claim 25 that encodes a polypeptide, module or domain derived from a chalcomycin polyketide synthase (PKS) gene cluster.
 27. A method of producing a polyketide, which method comprises growing the recombinant host cell of claim 17 or 24 under conditions whereby a polyketide synthesized by a PKS comprising a protein encoded by said recombinant DNA molecule is produced in the cell.
 28. The method of claim 27 further comprising recovering the synthesized polyketide.
 29. The method of claim 28 further comprising chemically modifying said polyketide.
 30. The method of claim 28 further comprising formulating said polyketide for administration to a mammal. 